Asymptomatic Helminth Infection in Active Tuberculosis Is Associated with Increased Regulatory and Th-2 Responses and a Lower Sputum Smear Positivity

Background

The impact of intestinal helminth infection on the clinical presentation and immune response during active tuberculosis (TB) infection is not well characterized. Our aim was to investigate whether asymptomatic intestinal helminth infection alters the clinical signs and symptoms as well as the cell mediated immune responses in patients with active TB.

Methodology

Consecutive, newly diagnosed TB patients and healthy community controls (CCs) were recruited in North-west Ethiopia. TB-score, body mass index and stool samples were analyzed. Cells from HIV-negative TB patients (HIV-/TB) and from CCs were analyzed for regulatory T-cells (Tregs) and cytokine responses using flow cytometry and ELISPOT, respectively.

Results

A significantly higher ratio of helminth co-infection was observed in TB patients without HIV (Helm+/HIV-/TB) compared to HIV negative CCs, (40% (121/306) versus 28% (85/306), p = 0.003). Helm+/HIV-/TB patients showed significantly increased IL-5 secreting cells compared to Helm-/HIV-/TB (37 SFU (IQR:13–103) versus 2 SFU (1–50); p = 0.02, n = 30). Likewise, levels of absolute Tregs (9.4 (3.2–16.7) cells/μl versus 2.4 (1.1–4.0) cells/μl; p = 0.041) and IL-10 secreting cells (65 SFU (7–196) versus 1 SFU (0–31); p = 0.014) were significantly higher in Helm+/HIV-/TB patients compared to Helm-/HIV-/TB patients. In a multivariate analysis, a lower rate of sputum smear positivity for acid fast bacilli, lower body temperature, and eosinophilia were independently associated with helminth infection in TB patients.

Conclusions

Asymptomatic helminth infection is associated with increased regulatory T-cell and Th2-type responses and a lower rate of sputum smear positivity. Further studies are warranted to investigate the clinical and immunological impact of helminth infection in TB patients.     

Helminth species dependent effects on Th1 and Th17 cytokines in active tuberculosis patients and healthy community controls

Despite that the impact of different helminth species is not well explored, the current dogma states that helminths affect the Th1/Th2 balance which in turn affects the risk of tuberculosis (TB) reactivation and severity of disease. We investigated the influence of helminth species on cytokine profiles including IL-17A in TB patients and healthy community controls (CCs). In total, 104 newly diagnosed pulmonary TB patients and 70 HIV negative and QuantiFERON negative CCs in Gondar, Ethiopia were included following helminth screening by stool microscopy. Plasma samples and ex vivo stimulation of peripheral blood mononuclear cells (PBMCs) with purified protein derivative (PPD) and Staphylococcus enterotoxin B (SEB) was used to determine cytokine profiles by cytometric bead array. In CCs, Ascaris lumbricoides or Schistosoma mansoni infections were associated with an impaired Th1-type response (IFN-gamma, IL-6 and TNF-alpha) in PBMCs mainly with SEB stimulations, whereas in TB patients only hookworm infection showed a similar pattern. Among CCs, the IL-17A response in PBMCs stimulated with SEB was higher only for S. mansoni, whereas in TB patients, the elevated systemic IL-17A plasma level was significantly suppressed in hookworm infected TB patients compared to patients without helminth coinfection. Following treatment of TB and helminth infection there was a general decrease in ex vivio IL-10 and TNF-alpha production in unstimulated, PPD or SEB stimulated PBMCs that was the most pronounced and significant in TB patients infected with S. mansoni, whereas the follow-up levels of IFN-gamma and IL-17A was significantly increased only in TB patients without helminth coinfection from PBMCs stimulated mainly with SEB. In summary, in addition to confirming helminth specific effects on the Th1/Th2 response before and after TB treatment, our novel finding is that IL-17A was impaired in helminth infected TB patients especially for hookworm, indicating a helminth species-specific immunoregulatory effect on IL-17A which needs to be further investigated.     

Helminth species specific expansion and increased TNF-alpha production of non-classical monocytes during active tuberculosis

Both Mycobacterium tuberculosis infection and helminths may affect innate immune mechanisms such as differential effects on monocytes towards the non-classical and intermediate subsets that favor bacterial persistence. Our aim, was to investigate helminth species specific effects on the frequency and functional activity of monocyte subsets in patients with active tuberculosis and healthy subjects. HIV-negative patients with active pulmonary tuberculosis (PTB) and community controls (CCs) in Gondar, Ethiopia were screened for helminth infection by stool microscopy. Flow cytometric analysis of peripheral blood mononuclear cells (PBMCs) and ex vivo stimulation with purified protein derivative (PPD) and helminth antigens were used to characterize the distribution of monocyte subsets and their function. A total of 74 PTB patients and 57 CCs with and without helminth infection were included. Non-classical monocytes were increased in PTB patients with Ascaris and hookworm infection but not in Schistosoma-infected patients. Ascaris had the strongest effect in increasing the frequency of non-classical monocytes in both PTB patients and CCs, whereas PTB without helminth infection did not affect the frequency of monocyte subsets. There was a helminth specific increase in the frequency of TNF-α producing non-classical monocytes in hookworm infected PTB patients, both with and without PPD-stimulation. Low-to-intermediate TB disease severity associated with increased frequency of non-classical monocytes only for helminth-positive PTB patients, and the frequency of TNF-α producing monocytes were significantly higher in intermediate and non-classical monocytes of helminth positive PTB patients with an intermediate disease score. Helminth infection affected the frequency of monocyte subsets and function both in TB patients and controls which was helminth species dependent in TB patients. The clinical role of this potential immunomodulatory effect needs further study and may affect the response and protection to tuberculosis in areas where helminth infections are endemic.     

Helminth Infections Coincident with Active Pulmonary Tuberculosis Inhibit Mono- and Multifunctional CD4+ and CD8+ T Cell Responses in a Process Dependent on IL-10

Tissue invasive helminth infections and tuberculosis (TB) are co-endemic in many parts of the world and can trigger immune responses that might antagonize each other. We have previously shown that helminth infections modulate the Th1 and Th17 responses to mycobacterial-antigens in latent TB. To determine whether helminth infections modulate antigen-specific and non-specific immune responses in active pulmonary TB, we examined CD4⁺ and CD8⁺ T cell responses as well as the systemic (plasma) cytokine levels in individuals with pulmonary TB with or without two distinct helminth infections—Wuchereria bancrofti and Strongyloides stercoralis infection. By analyzing the frequencies of Th1 and Th17 CD4⁺ and CD8⁺ T cells and their component subsets (including multifunctional cells), we report a significant diminution in the mycobacterial–specific frequencies of mono- and multi–functional CD4⁺ Th1 and (to a lesser extent) Th17 cells when concomitant filarial or Strongyloides infection occurs. The impairment in CD4⁺ and CD8⁺ T cell cytokine responses was antigen-specific as polyclonal activated T cell frequencies were equivalent irrespective of helminth infection status. This diminution in T cell responses was also reflected in diminished circulating levels of Th1 (IFN-γ, TNF-α and IL-2)- and Th17 (IL-17A and IL-17F)-associated cytokines. Finally, we demonstrate that for the filarial co-infections at least, this diminished frequency of multifunctional CD4⁺ T cell responses was partially dependent on IL-10 as IL-10 blockade significantly increased the frequencies of CD4⁺ Th1 cells. Thus, co-existent helminth infection is associated with an IL-10 mediated (for filarial infection) profound inhibition of antigen-specific CD4⁺ T cell responses as well as protective systemic cytokine responses in active pulmonary TB.     

The impact of asymptomatic helminth co-infection in patients with newly diagnosed tuberculosis in north-west ethiopia

Background

Areas endemic of helminth infection, tuberculosis (TB) and HIV are to a large extent overlapping. The aim of this study was to assess the impact of asymptomatic helminth infection on the immunological response among TB patients with and without HIV, their house hold contacts and community controls.

Methodology

Consecutive smear positive TB patients (n = 112), their household contacts (n = 71) and community controls (n = 112) were recruited in Gondar town, Ethiopia. Stool microscopy, HIV serology, serum IgE level, eosinophil and CD4 counts were performed and tuberculosis patients were followed up for 3 months after initiation of anti-TB treatment.

Results

Helminth co-infection rate was 29% in TB patients and 21% in both community control and household contacts (p = 0.3) where Ascaris lumbricoides was the most prevalent parasite. In TB patients the seroprevalence of HIV was 47% (53/112). Eosinophilia and elevated IgE level were significantly associated with asymptomatic helminth infection. During TB treatment, the worm infection rate of HIV+/TB patients declined from 31% (10/32) at week 0 to 9% (3/32) at week 2 of TB treatment, whereas HIV−/TB patients showed no change from baseline to week 2, 29% (13/45) vs. 22.2% (10/45). This trend was stable at week 8 and 12 as well.

Conclusion

One third of smear positive TB patients were infected with helminths. Eosinophilia and elevated IgE level correlated with asymptomatic worm infection, indicating an effect on host immunity. The rate of worm infection declined during TB treatment in HIV+/TB co-infected patients whereas no decline was seen in HIV−/TB group.     

Intraepithelial NK cell-derived IL-13 induces intestinal pathology associated with nematode infection

IL-13 is a Th2-derived cytokine associated with pathological changes in asthma and ulcerative colitis. Moreover, it plays a major role in the control of gut nematode infection and associated immunopathology. The current paradigm is that these effects are due to T cell-derived IL-13. We show in this study that an innate source of IL-13, the intraepithelial NK cell, is responsible for the disruption of intestinal tissue architecture and induction of goblet cell hyperplasia that characterizes infection with the intestinal helminth Trichinella spiralis. IL-13 or IL-4Ralpha (but not IL-4) null mice failed to induce intestinal pathology. Unexpectedly, SCID and athymic mice developed the same pathology found in immunocompetent mice following infection. Moreover, immunodeficient mice expressed IL-13 in the intestine, and abnormal mucosal pathology was reduced by in vivo administration of a soluble IL-13 antagonist. IL-13 expression was induced in non-T intraepithelial CD3- NK cells. Epithelial cells expressed the IL-13 signaling receptor, IL-13Ralpha1, and after infection, IL-4Ralpha. Furthermore, the soluble IL-13 decoy receptor IL-13Ralpha2, which regulates IL-13 responses, was also induced upon infection. These data provide the first evidence that intestinal tissue restructuring during helminth infection is an innate event dependent on IL-13 production by NK cells resident in the epithelium of the intestine.     

Plasmodium/intestinal helminth co-infections among pregnant Nigerian women.

Hospital based studies were conducted to investigate the occurrence of Plasmodium/intestinal helminth co-infections among pregnant Nigerian women, and their effects on birthweights, anaemia and spleen size. From 2,104 near-term pregnant women examined, 816 (38.8%) were found to be infected with malaria parasites. Among the 816 parasitaemic subjects, 394 (48.3%) were also infected with intestinal helminths, 102 (12.5%) having mixed helminth infections. The prevalence of the helminth species found in stool samples of parasitaemic subjects examined was, Ascaris lumbricoides (19.1%), hookworm (14.2%), Trichuris trichiura (7%) Schistosoma mansoni (3.4%), Enterobius vermicularis (2%), Hymenolepis sp. (1.6%) and Taenia sp. (1%). Mothers with Plasmodium infection but without intestinal helminth infection had neonates of higher mean birthweights than those presenting both Plasmodium and intestinal helminth infections and this effect was more pronounced in primigravids. The mean haemoglobin values of malarial mothers with intestinal helminth infections were lower than those with Plasmodium infection but without intestinal helminth infections but these were not statistically significant. Severe splenomegaly was predominant among parasitaemic gravidae who also harboured S. mansoni infection in two of the hospitals studied.     

Context-dependent roles of B cells during intestinal helminth infection

The current approaches to reduce the burden of chronic helminth infections in endemic areas are adequate sanitation and periodic administration of deworming drugs. Yet, resistance against some deworming drugs and reinfection can still rapidly occur even after treatment. A vaccine against helminths would be an effective solution at preventing reinfection. However, vaccines against helminth parasites have yet to be successfully developed. While T helper cells and innate lymphoid cells have been established as important components of the protective type 2 response, the roles of B cells and antibodies remain the most controversial. Here, we review the roles of B cells during intestinal helminth infection. We discuss the potential factors that contribute to the context-specific roles for B cells in protection against diverse intestinal helminth parasite species, using evidence from well-defined murine model systems. Understanding the precise roles of B cells during resistance and susceptibility to helminth infection may offer a new perspective of type 2 protective immunity.     

The Effect of Maternal Helminth Infection on Maternal and Neonatal Immune Function and Immunity to Tuberculosis

Background

M. tuberculosis and helminth infection each affects one third of the world population. Helminth infections down regulate cell mediated immune responses and this may contribute to lower efficacy of BCG vaccination and higher prevalence of tuberculosis.

Objective

To determine the effect of maternal helminth infection on maternal and neonatal immune function and immunity to TB.

Methods

In this cross sectional study, eighty five pregnant women were screened for parasitic and latent TB infections using Kato-Katz and QFT-GIT tests, respectively. IFN-γ and IL-4 ELISpot on Cord blood Mononuclear Cells, and total IgE and TB specific IgG ELISA on cord blood plasma was performed to investigate the possible effect of maternal helminth and/or latent TB co-infection on maternal and neonatal immune function and immunity to TB.

Result

The prevalence of helminth infections in pregnant women was 27% (n = 23), with Schistosoma mansoni the most common helminth species observed (20% of women were infected). Among the total of 85 study participants 25.8% were QFT-GIT positive and 17% had an indeterminate result. The mean total IgE value of cord blood was significantly higher in helminth positive than negative women (0.76 vs 0.47, p = 0.042). Cross placental transfer of TB specific IgG was significantly higher in helminth positive (21.9±7.9) than negative (12.3±5.1), p = 0.002) Latent TB Infection positive participants. The IFN-γ response of CBMCs to ESAT-6/CFP-10 cocktail (50 vs 116, p = 0.018) and PPD (58 vs 123, p = 0.02) was significantly lower in helminth positive than negative participants. There was no significant difference in IL-4 response of CBMCs between helminth negative and positive participants.

Conclusions

Maternal helminth infection had a significant association with the IFN-γ response of CBMCs, total IgE and cross placental transfer of TB specific IgG. Therefore, further studies should be conducted to determine the effect of these factors on neonatal immune response to BCG vaccination.     

Intestinal helminths in a population of children from the Kashmir valley, India

In any geographical area, surveys of the prevalence of intestinal helminths are necessary to suggest appropriate control measures. The aim of this study was to determine the prevalence of intestinal helminth infections in children of the Kashmir valley and to identify the risk factors. Stool samples were collected from 2256 children from rural as well as urban areas of the Kashmir valley. The samples were examined by simple smear and zinc sulphate concentration methods. Intensity of the infection was quantified by Stoll's egg-counting technique. Infection by at least one intestinal helminth was found in 71.18% of the sampled population. The prevalence of Ascaris lumbricoides was highest (68.30%), followed by Trichuris trichiura (27.92%), Enterobius vermicularis (12.67%) and Taenia saginata (4.60%). Light (57.1%) to moderate (42.8%) intensity of infection was observed for A. lumbricoides, while the majority of the infected children (92.3%) harboured a light intensity of infection for T. trichiura. The age group, rural or urban residence, type of water source, boiled or unboiled water, type of defecation site, level of personal hygiene and maternal education were associated with helminth infection. Adequate control measures are urgently needed to combat the high prevalence of intestinal helminths and risk factors in the children of Kashmir valley.     

Helminth-primed dendritic cells alter the host response to enteric bacterial infection

To examine whether intestinal helminth infection may be a risk factor for enteric bacterial infection, a murine model was established using the intestinal helminth Heligomosomoides polygyrus and a murine pathogen Citrobacter rodentium, which causes infectious colitis. Using this model we recently have shown that coinfection with the Th2-inducing H. polygyrus and C. rodentium promotes bacterial-associated disease and colitis. In this study, we expand our previous observations and examine the hypothesis that dendritic cells (DC) stimulated by helminth infection may play an important role in the regulation of the intestinal immune response to concurrent C. rodentium infection as well as in the modulation of the bacterial pathogenesis. We show that H. polygyrus infection induces DC activation and IL-10 expression, and that adoptive transfer of parasite-primed DC significantly impairs host protection to C. rodentium infection, resulting in an enhanced bacterial infection and in the development of a more severe colonic injury. Furthermore, we demonstrate that adoptive transfer of parasite-primed IL-10-deficient DCs fails to result in the development of a significantly enhanced C. rodentium-mediated colitis. Similarly, when the DC IL-10 response was neutralized by anti-IL-10 mAb treatment in mice that received parasite-primed DC, no deleterious effect of the parasite-primed DC on the host intestinal response to C. rodentium was detected. Thus, our results provide evidence to indicate that the H. polygyrus-dependent modulation of the host response to concurrent C. rodentium infection involves IL-10-producing DCs.     

Coincident Helminth Infection Modulates Systemic Inflammation and Immune Activation in Active Pulmonary Tuberculosis

Background

Helminth infections are known to modulate innate and adaptive immune responses in active and latent tuberculosis (TB). However, the role of helminth infections in modulating responses associated with inflammation and immune activation (reflecting disease activity and/or severity) in TB is not known.

Methodology

We measured markers of inflammation and immune activation in active pulmonary TB individuals (ATB) with co-incidental Strongyloides stercoralis (Ss) infection. These included systemic levels of acute phase proteins, matrix metalloproteinases and their endogenous inhibitors and immune activation markers. As a control, we measured the systemic levels of the same molecules in TB-uninfected individuals (NTB) with or without Ss infection.

Principal Findings

Our data confirm that ATB is associated with elevated levels of the various measured molecules when compared to those seen in NTB. Our data also reveal that co-incident Ss infection in ATB individuals is associated with significantly decreased circulating levels of acute phase proteins, matrix metalloproteinases, tissue inhibitors of matrix metalloproteinases as well as the systemic immune activation markers, sCD14 and sCD163. These changes are specific to ATB since they are absent in NTB individuals with Ss infection.

Conclusions

Our data therefore reveal a profound effect of Ss infection on the markers associated with TB disease activity and severity and indicate that co-incidental helminth infections might dampen the severity of TB disease.     

IL-10- and TGFβ-mediated Th9 Responses in a Human Helminth Infection

Background

Th9 cells are a subset of CD4⁺ T cells that express the protoypical cytokine, IL-9. Th9 cells are known to effect protective immunity in animal models of intestinal helminth infections. However, the role of Th9 cells in human intestinal helminth infections has never been examined.

Methodology

To examine the role of Th9 cells in Strongyloidis stercoralis (Ss), a common intestinal helminth infection, we compared the frequency of Th9 expressing IL-9 either singly (mono-functional) or co-expressing IL-4 or IL-10 (dual-functional) in Ss-infected individuals (INF) to frequencies in uninfected (UN) individuals.

Principal Findings

INF individuals exhibited a significant increase in the spontaneously expressed and/or antigen specific frequencies of both mono- and dual-functional Th9 cells as well as Th2 cells expressing IL-9 compared to UN. The differences in Th9 induction between INF and UN individuals was predominantly antigen-specific as the differences were no longer seen following control antigen or mitogen stimulation. In addition, the increased frequency of Th9 cells in response to parasite antigens was dependent on IL-10 and TGFx since neutralization of either of these cytokines resulted in diminished Th9 frequencies. Finally, following successful treatment of Ss infection, the frequencies of antigen-specific Th9 cells diminished in INF individuals, suggesting a role for the Th9 response in active Ss infection. Moreover, IL-9 levels in whole blood culture supernatants following Ss antigen stimulation were higher in INF compared to UN individuals.

Conclusion

Thus, Ss infection is characterized by an IL-10- and TGFβ dependent expansion of Th9 cells, an expansion found to reversible by anti-helmintic treatment.     

Goblet cell-derived resistin-like molecule beta augments CD4+ T cell production of IFN-gamma and infection-induced intestinal inflammation

The secreted goblet cell-derived protein resistin-like molecule beta (RELMbeta) has been implicated in divergent functions, including a direct effector function against parasitic helminths and a pathogenic function in promoting inflammation in models of colitis and ileitis. However, whether RELMbeta influences CD4(+) T cell responses in the intestine is unknown. Using a natural model of intestinal inflammation induced by chronic infection with gastrointestinal helminth Trichuris muris, we identify dual functions for RELMbeta in augmenting CD4(+) Th1 cell responses and promoting infection-induced intestinal inflammation. Following exposure to low-dose Trichuris, wild-type C57BL/6 mice exhibit persistent infection associated with robust IFN-gamma production and intestinal inflammation. In contrast, infected RELMbeta(-/-) mice exhibited a significantly reduced expression of parasite-specific CD4(+) T cell-derived IFN-gamma and TNF-alpha and failed to develop Trichuris-induced intestinal inflammation. In in vitro T cell differentiation assays, recombinant RELMbeta activated macrophages to express MHC class II and secrete IL-12/23p40 and enhanced their ability to mediate Ag-specific IFN-gamma expression in CD4(+) T cells. Taken together, these data suggest that goblet cell-macrophage cross-talk, mediated in part by RELMbeta, can promote adaptive CD4(+) T cell responses and chronic inflammation following intestinal helminth infection.     

A hybrid multi-compartment model of granuloma formation and T cell priming in tuberculosis

Tuberculosis is a worldwide health problem with 2 billion people infected with Mycobacterium tuberculosis (Mtb, the bacteria causing TB). The hallmark of infection is the emergence of organized structures of immune cells forming primarily in the lung in response to infection. Granulomas physically contain and immunologically restrain bacteria that cannot be cleared. We have developed several models that spatially characterize the dynamics of the host-mycobacterial interaction, and identified mechanisms that control granuloma formation and development. In particular, we published several agent-based models (ABMs) of granuloma formation in TB that include many subtypes of T cell populations, macrophages as well as key cytokine and chemokine effector molecules. These ABM studies emphasize the important role of T-cell related mechanisms in infection progression, such as magnitude and timing of T cell recruitment, and macrophage activation. In these models, the priming and recruitment of T cells from the lung draining lymph node (LN) was captured phenomenologically. In addition to these ABM studies, we have also developed several multi-organ models using ODEs to examine trafficking of cells between, for example, the lung and LN. While we can predict temporal dynamic behaviors, those models are not coupled to the spatial aspects of granuloma. To this end, we have developed a multi-organ model that is hybrid: an ABM for the lung compartment and a non-linear system of ODE representing the lymph node compartment. This hybrid multi-organ approach to study TB granuloma formation in the lung and immune priming in the LN allows us to dissect protective mechanisms that cannot be achieved using the single compartment or multi-compartment ODE system. The main finding of this work is that trafficking of important cells known as antigen presenting cells from the lung to the lymph node is a key control mechanism for protective immunity: the entire spectrum of infection outcomes can be regulated by key immune cell migration rates. Our hybrid multi-organ implementation suggests that effector CD4+ T cells can rescue the system from a persistent infection and lead to clearance once a granuloma is fully formed. This could be effective as an immunotherapy strategy for latently infected individuals.     

Alternatively activated macrophages in intestinal helminth infection: effects on concurrent bacterial colitis

The distribution of several pathogenic helminth infections coincides geographically with many devastating microbial diseases, including enteric bacterial infections. To dissect the mechanisms by which helminths modulate the host's response to enteric bacteria and bacteria-mediated intestinal inflammation, we have recently established a coinfection model and shown that coinfection with the helminth Heligmosomoides polygyrus exacerbates colitis induced by infection with the gram-negative bacterial pathogen Citrobacter rodentium. The disease severity of the coinfected mice was correlated with high Citrobacter loads in the gut, translocation of the bacteria into mucosal and systemic immune compartments, delayed bacterial clearance, and a significantly enhanced colonic TNF-alpha response. In the present study, using our in vivo coinfection model as well as in vitro approaches, we test the hypothesis that the phenotypic and functional alterations in macrophages induced by the helminth-driven T cell response may contribute to the observed alterations in the response to C. rodentium. We show that via a STAT6-dependent mechanism H. polygyrus coinfection results in a marked infiltration into the colonic lamina propria of F4/80+ cells that have the phenotype of alternatively activated macrophages. Functional analysis of these macrophages further shows that they are impaired in their killing of internalized bacteria. Yet, these cells produce an enhanced amount of TNF-alpha in response to C. rodentium infection. These results demonstrate that helminth infection can impair host protection against concurrent enteric bacterial infection and promote bacteria-induced intestinal injury through a mechanism that involves the induction of alternatively activated macrophages.     

Age-dependent epidemiological patterns and strain diversity in helminth parasites

Field studies of schistosomes and the major intestinal nematodes Trichuris trichiura and Ascaris lumbricoides repeatedly demonstrate that the intensity and prevalence of infection exhibit marked dependency on host age. Peak levels of infection typically occur in hosts aged between 10 and 14 yr in endemically infected communities. It has widely been assumed that the slow acquisition of resistance in adults is caused by repeated exposure to the same antigenic repertoire of a single parasite strain. Consequently, these empirical patterns have previously been taken to suggest that human immunity to helminth parasites confers poor protection against reinfection. Here, an alternative explanation is suggested on the basis of results from a simplified model of helminth transmission. It is proposed that the empirical observations can be attributed to the circulation of multiple helminth strains that each elicit highly protective immunity. If this hypothesis is correct, estimates of epidemiological parameters from field data and the potential for control of helminth diseases might require reevaluation.     

The intestinal parasite infection status of inhabitants in the Roxas city,The Philippines

We carried out a small-scale survey to investigate the status of intestinal protozoa and helminthes infection of inhabitants in Roxas city, Mindoro, the Philippines. Total 301 stool samples were subjected to the formalin-ether concentration method for the detection of helminth ova and protozoan cysts. The overall positive rate was 64.5%, and that of male and female were 56.6% and 72.5%, respectively. The highest infected helminth was Ascaris lumbricoudes (51.2%), followed by Trichuris trichiura (27.6%), hookworm (8.0%) and Enterobius vermicularis (0.3%). The protozoa infection status revealed that Entamoeba coli was the most frequent (15.0%). Iodoamoeba buetschlii and E. histolytica were found but few. The multiple infection more than two parasites was 29.6%, and double infection with A. lumbricoides and T. trichiura was most common. The intestinal helminth infections were highly prevalent in this area, according to this result, and we concluded that anthelminthic drugs should be given to inhabitants, especially to children of 1 to 15 years-old.     

Helminth parasites of Clarias gariepinus (Clariidae) in Lekki Lagoon, Lagos, Nigeria

A total of 360 randomly selected specimens of Clarias gariepinus (Clariidae) recovered from Lekki Lagoon were examined for intestinal helminth parasites. Parasite prevalence and worm burden were low; 17 (4.72%) of the specimens examined were infected with gastrointestinal helminths. The helminth worms recovered include, three cestodes Polyonchobothrium clarias, Stocksia pujehuni and Wenyonia acuminata and a nematode, Paracamallanus cyathopharynx. There was no statistically significant difference in the infection of the male and female Clarias gariepinus; the infection rates in male and female samples were 5.75% and 3.76% respectively. Parasite prevalence was related to the length and weight of the specimens. The fish samples were observed to show negative allometric growth and smaller samples recorded higher helminth infection.     

Assessing the role of CD103 in immunity to an intestinal helminth parasite

Background

In the intestine, the integrin CD103 is expressed on a subset of T regulatory (T_reg) cells and a population of dendritic cells (DCs) that produce retinoic acid and promote immune homeostasis. However, the role of CD103 during intestinal helminth infection has not been tested.

Methodology/Principal Findings

We demonstrate that CD103 is dispensable for the development of protective immunity to the helminth parasite Trichuris muris. While we observed an increase in the frequency of CD103⁺ DCs in the lamina propria (LP) following acute high-dose infection with Trichuris, lack of CD103 had no effect on the frequency of CD11c⁺ DCs in the LP or mesenteric lymph nodes (mLN). CD103-deficient (CD103^−/−) mice develop a slightly increased and earlier T cell response but resolve infection with similar kinetics to control mice. Similarly, low-dose chronic infection of CD103^−/− mice with Trichuris resulted in no significant difference in immunity or parasite burden. Absence of CD103 also had no effect on the frequency of CD4⁺CD25⁺Foxp3⁺ T_reg cells in the mLN or LP.

Conclusions/Significance

These results suggest that CD103 is dispensable for intestinal immunity during helminth infection. Furthermore, lack of CD103 had no effect on DC or T_reg recruitment or retention within the large intestine.