Dexamethasone reduces bronchial wall remodeling during pulmonary migration of Strongyloides venezuelensis larvae in rats

Strongyloidiasis is an intestinal parasitosis with an obligatory pulmonary cycle. A Th2-type immune response is induced and amplifies the cellular response through the secretion of inflammatory mediators. Although this response has been described as being similar to asthma, airway remodeling during pulmonary migration of larvae has not yet been established. The aim of this study was to identify the occurrence of airway remodeling during Strongyloides venezuelensis (S. v.) infection and to determine the ability of dexamethasone treatment to interfere with the mechanisms involved in this process. Rats were inoculated with 9,000 S. v. larvae, treated with dexamethasone (2 mg/kg) and killed at 1, 3, 5, 7, 14 and 21 days. Morphological and morphometric analyzes with routine stains and immunohistochemistry were conducted, and some inflammatory mediators were evaluated using ELISA. Goblet cell hyperplasia and increased bronchiolar thickness, characterized by edema, neovascularization, inflammatory infiltrate, collagen deposition and enlargement of the smooth muscle cell layer were observed. VEGF, IL1-β and IL-4 levels were elevated throughout the course of the infection. The morphological findings and the immunomodulatory response to the infection were drastically reduced in dexamethasone-treated rats. The pulmonary migration of S. venezuelensis larvae produced a transitory, but significant amount of airway remodeling with a slight residual bronchiolar fibrosis. The exact mechanisms involved in this process require further study.     

Antigen, antibody and immune complex detection in serum samples from rats experimentally infected with Strongyloides venezuelensis

In order to establish an antigen, antibody and immune complex detection by enzyme-linked immunosorbent assay (ELISA) in serum samples, normal or immunocompromised Wistar rats experimentally infected with Strongyloides venezuelensis were used. The microtitre plates were coated with IgG anti-S. venezuelensis for antigen and immune complex detection and with alkaline parasite extract for antibody detection. Analysis revealed at least 12.5 μg/mL of S. venezuelensis specific antigens in serum samples. Assay for antigen detection was not a good approach for evaluating infection in normal or immunocompromised rats. In normal rats IgG specific for S. venezuelensis was preferentially detected during the first 13 days post-infection (p.i.) and immune complex detection was significantly reduced in 21 p.i. day. On the other hand, in immunocompromised rats, IgG and immune complex were detected during the entire kinetic (5, 8, 13 and 21 p.i). These results suggest that immune complex screening seems to be an alternative for early strongyloidiasis diagnosis in immunocompromised individuals.     

Chlamydia muridarum Lung Infection in Infants Alters Hematopoietic Cells to Promote Allergic Airway Disease in Mice

Background

Viral and bacterial respiratory tract infections in early-life are linked to the development of allergic airway inflammation and asthma. However, the mechanisms involved are not well understood. We have previously shown that neonatal and infant, but not adult, chlamydial lung infections in mice permanently alter inflammatory phenotype and physiology to increase the severity of allergic airway disease by increasing lung interleukin (IL)-13 expression, mucus hyper-secretion and airway hyper-responsiveness. This occurred through different mechanisms with infection at different ages. Neonatal infection suppressed inflammatory responses but enhanced systemic dendritic cell:T-cell IL-13 release and induced permanent alterations in lung structure (i.e., increased the size of alveoli). Infant infection enhanced inflammatory responses but had no effect on lung structure. Here we investigated the role of hematopoietic cells in these processes using bone marrow chimera studies.

Methodology/Principal Findings

Neonatal (<24-hours-old), infant (3-weeks-old) and adult (6-weeks-old) mice were infected with C. muridarum. Nine weeks after infection bone marrow was collected and transferred into recipient age-matched irradiated naïve mice. Allergic airway disease was induced (8 weeks after adoptive transfer) by sensitization and challenge with ovalbumin. Reconstitution of irradiated naïve mice with bone marrow from mice infected as neonates resulted in the suppression of the hallmark features of allergic airway disease including mucus hyper-secretion and airway hyper-responsiveness, which was associated with decreased IL-13 levels in the lung. In stark contrast, reconstitution with bone marrow from mice infected as infants increased the severity of allergic airway disease by increasing T helper type-2 cell cytokine release (IL-5 and IL-13), mucus hyper-secretion, airway hyper-responsiveness and IL-13 levels in the lung. Reconstitution with bone marrow from infected adult mice had no effects.

Conclusions

These results suggest that an infant chlamydial lung infection results in long lasting alterations in hematopoietic cells that increases the severity of allergic airway disease in later-life.     

IL-27 suppresses Th2 cell development and Th2 cytokines production from polarized Th2 cells: a novel therapeutic way for Th2-mediated allergic inflammation

IL-27 up-regulates Th1 but down-regulates Th2 responses. However, its molecular mechanism and regulatory effects on polarized Th2 cells remain unclear. In this study, we have revealed that IL-27 inhibits Th2 cell development as well as Th2 cytokines production from already polarized Th2 cells by down-regulation of GATA-3 and up-regulation of T-bet expression simultaneously. In vivo daily IL-27 treatment for 1 wk after Leishmania major infection protects BALB/c mice from footpad swelling by diminishing parasite burden via reciprocal regulation of Th1 and Th2 responses. Furthermore, IL-27 stimulation causes marked reduction in the capacity of host mouse to mount a Th2 response against Strongyloides venezuelensis infection. Thus, IL-27-treated mice failed to develop intestinal mastocytosis after S. venezuelensis infection and exhibited a marked delay in parasite expulsion. Finally, intranasal administration of IL-27 inhibits OVA-induced airway hyperresponsiveness and inflammation in OVA-sensitized animals. Thus, IL-27 could provide us with a novel therapeutic way for treating Th2-associated diseases such as bronchial asthma.     

Leukotrienes play a role in the control of parasite burden in murine strongyloidiasis

It is clear that leukotrienes mediate inflammatory response; new aspects of leukotriene function have recently been described. In this study, we demonstrate that leukotrienes are key chemical mediators in the control of parasite burdens in mice infected with Strongyloides venezuelensis. High leukotriene levels were detected in the lungs and small intestines of Swiss mice. In infected Swiss mice treated with MK886, a leukotriene synthesis inhibitor, numbers of adult worms, and eggs/g/feces were greater than in infected-only animals. The MK886 treatment inhibited leukotriene B(4) production in the lungs and small intestines, albeit on different postinfection days. Similarly, parasite burdens and eggs/g/feces were greater in 5-lipoxygenase(-/-) mice than in wild-type animals. These observation were confirmed by histopathological study of the duodena. We subsequently observed significant lower numbers of eosinophils and mononuclear cells in the blood, peritoneal cavity fluid, and bronchoalveolar lavage fluid of Swiss mice treated with MK886. In the lung parenchyma of infected animals, MK886 significantly inhibited synthesis of IL-5 at the beginning of infection, whereas levels of IL-12 increased progressively throughout the postinfection period. However, levels of leukotriene C(4), PGE(2), TNF-alpha, IL-3, IL-4, IFN-gamma, and IL-10 were comparable between the treated and untreated groups. Nevertheless, IgE and IgG1 (but not IgG2a) synthesis was also significantly inhibited by MK886 administration. Therefore, in S. venezuelensis-infected mice, adult worm and egg burdens are leukotriene dependent. These findings indicate potential immunostimulatory strategies involving leukotriene administration, and may serve as an alert to physicians treating Strongyloides stercoralis-infected patients presenting asthma-like symptoms because use of 5-lipoxygenase inhibitors may worsen the infection.     

Protection against Nippostrongylus brasiliensis infection in mice is independent of GM-CSF

Granulocyte macrophage-colony stimulating factor (GM-CSF) is a cytokine with the capacity to promote inflammation in a wide variety of infectious and inflammatory diseases. These conditions include allergic airway inflammation, which is driven by T-helper 2 (Th2) cells. Because of the importance of Th2 cells in parasite infections, we have investigated the role of GM-CSF in mice infected with the nematode Nippostrongylus brasiliensis. The effect of primary and secondary infection was investigated in mice lacking functional genes for GM-CSF (CSF2 genes) (ΔGM-CSF mice), and in mice lacking the cytokine receptor common β chain (Δβ mice), the latter being unable to signal in response to GM-CSF and interleukin (IL)-5. ΔGM-CSF mice showed no significant defect in parasite immunity, measured by larval numbers in the lungs, worm numbers in the intestine or egg numbers in the faeces, in either primary or secondary infection. By contrast, the Δβ mice showed increased parasite burden, with higher numbers of lung larvae after secondary infection and higher numbers of intestinal worms and faecal eggs after both primary and secondary infection. Unexpectedly, there were increased numbers of circulating eosinophils in the ΔGM-CSF mice, associated with significantly reduced larval numbers in the lungs. These results indicate that GM-CSF is redundant in protection against N. brasiliensis infection, and that the increased susceptibility of Δβ mice to infection is likely to be attributed to the lack of IL-5 signalling in these mice. The results suggest that clinical use of agents that neutralise GM-CSF may not be associated with increased risk of parasite infection.     

Expression of IL-4 receptor on non-bone marrow-derived cells is necessary for the timely elimination of Strongyloides venezuelensis in mice, but not for intestinal IL-4 production

In rodents and in humans, Strongyloides infection induces an immune response which is predominantly Th2 in nature. In an attempt to understand the role of the IL-4R/STAT6 signaling pathway, the pathway activated by the Th2 cytokines IL-4 and IL-13, in the induction of protection during Strongyloides venezuelensis infection, we have carried out experiments in mice lacking the IL-4Ralpha chain. Experiments were also carried out in STAT6 (STAT6(-/-)) and IL-12-deficient (IL-12(-/-)) mice for comparison. There was enhancement of IL-13 and abolition of IFN-gamma production in the small intestine of 7 day-infected IL-12(-/-) animals but worm elimination proceeded with very similar kinetics to those of wild-type mice. In IL-4Ralpha- or STAT6-deficient mice, there was a delay in parasite elimination and a large number of S. venezuelensis adult worms was still present in the small intestine 14 days after infection. Moreover, IgE production was completely abolished in IL-4Ralpha- or STAT6-deficient mice but tissue eosinophilia was normally induced by the parasite infection in deficient mice. Bone marrow transfer experiments showed that worm elimination occurred when a functional IL-4 receptor was present only in non-bone marrow-derived cells but not when IL-4R was only expressed in bone marrow cells. The induction of IL-4, but not IL-13, occurred independently of IL-4R. We believe these results are the first direct evidence that the mechanism responsible for the timely elimination of S. venezuelensis is dependent on the activation of IL-4R and STAT6. Moreover, a functional protective response is dependent on the expression of IL-4Ralpha on non-bone marrow-derived cells.     

The enhancement or prevention of airway hyperresponsiveness during reinfection with respiratory syncytial virus is critically dependent on the age at first infection and IL-13 production

Respiratory syncytial virus (RSV) infection in early life is suspected to play a role in the development of post-bronchiolitis wheezing and asthma. Reinfection is common at all ages, but factors that determine the development of altered airway function after reinfection are not well understood. This study was conducted in a mouse model to define the role of age in determining the consequences on airway function after reinfection. Mice were infected shortly after birth or at weaning and were reinfected 5 wk later, followed by assessment of airway function, airway inflammation, and lung histopathology. Infection of mice at weaning elicited a protective airway response upon reinfection. In this age group, reinfection resulted in increased airway inflammation, but without development of airway hyperresponsiveness (AHR) or eosinophilia and decreased IL-13 levels. By contrast, neonatal infection failed to protect the airways and resulted in enhanced AHR after reinfection. This secondary response was associated with the development of airway eosinophilia, increased IL-13 levels, and mucus hyperproduction. Both CD4- and CD8-positive T cells were a source of IL-13 in the lung, and inhibition of IL-13 abolished AHR and mucus production in these mice. Inoculation of UV-inactivated virus failed to elicit these divergent responses to reinfection, emphasizing the requirement for active lung infection during initial exposure. Thus, neonatal RSV infection predisposes to the development of airway eosinophilia and enhanced AHR via an IL-13-dependent mechanism during reinfection, whereas infection at a later age protects against the development of these altered airway responses after reinfection.     

Migratory route of Strongyloides venezuelensis in Lewis rats: Comparison of histological analyses and PCR

Strongyloides venezuelensis is a parasitic nematode that has been used as a model to study human and animal strongyloidiasis. In this study, we compared the sensitivity between traditional methodologies and PCR assay to characterize the dynamics of S. venezuelensis infection and its migration route in Lewis rats subcutaneously infected with 4000 L3. The dynamics of the infection was determined by counting the number of eggs and by detecting parasite deoxyribonucleic acid in faeces samples. Both techniques similarly detected the infection at day 6 after larvae inoculation. However, PCR performed with the genus primer showed higher sensitivity during the recovery phase. Histological analysis and PCR assay were then used to follow parasite tissue migration. S. venezuelensis migration route included the muscular fibers below the skin, the pulmonary alveoli and the small intestine vilosities. The sensitivity of these two techniques to detect parasite’s presence in these tissues was statistically similar.     

Multiple Exposures to Ascaris suum Induce Tissue Injury and Mixed Th2/Th17 Immune Response in Mice

Ascaris spp. infection affects 800 million people worldwide, and half of the world population is currently at risk of infection. Recurrent reinfection in humans is mostly due to the simplicity of the parasite life cycle, but the impact of multiple exposures to the biology of the infection and the consequences to the host’s homeostasis are poorly understood. In this context, single and multiple exposures in mice were performed in order to characterize the parasitological, histopathological, tissue functional and immunological aspects of experimental larval ascariasis. The most important findings revealed that reinfected mice presented a significant reduction of parasite burden in the lung and an increase in the cellularity in the bronchoalveolar lavage (BAL) associated with a robust granulocytic pulmonary inflammation, leading to a severe impairment of respiratory function. Moreover, the multiple exposures to Ascaris elicited an increased number of circulating inflammatory cells as well as production of higher levels of systemic cytokines, mainly IL-4, IL-5, IL-6, IL-10, IL-17A and TNF-α when compared to single-infected animals. Taken together, our results suggest the intense pulmonary inflammation associated with a polarized systemic Th2/Th17 immune response are crucial to control larval migration after multiple exposures to Ascaris.     

Mixed infection and clonal representativeness of a single sputum sample in tuberculosis patients from a penitentiary hospital in Georgia

Background

Respiratory syncytial virus (RSV) is the most common cause of acute bronchiolitis in infants and the elderly. Furthermore, epidemiological data suggest that RSV infection during infancy is a potent trigger of subsequent wheeze and asthma development. However, the mechanism by which RSV contributes to asthma is complex and remains largely unknown. A recent study indicates that the age of initial RSV infection is a key factor in determining airway response to RSV rechallenge. We hypothesized that severe RSV infection during neonatal development significantly alters lung structure and the pulmonary immune micro-environment; and thus, neonatal RSV infection is crucial in the development of or predisposition to allergic inflammatory diseases such as asthma.

Methods

To investigate this hypothesis the present study was conducted in a neonatal mouse model of RSV-induced pulmonary inflammation and airway dysfunction. Seven-day-old mice were infected with RSV (2 × 10⁵ TCID₅₀/g body weight) and allowed to mature to adulthood. To determine if neonatal RSV infection predisposed adult animals to enhanced pathophysiological responses to allergens, these mice were then sensitized and challenged with ovalbumin. Various endpoints including lung function, histopathology, cytokine production, and cellularity in bronchoalveolar lavage were examined.

Results

RSV infection in neonates alone led to inflammatory airway disease characterized by airway hyperreactivity, peribronchial and perivascular inflammation, and subepithelial fibrosis in adults. If early RSV infection was followed by allergen exposure, this pulmonary phenotype was exacerbated. The initial response to neonatal RSV infection resulted in increased TNF-α levels in bronchoalveolar lavage. Interestingly, increased levels of IL-13 and mucus hyperproduction were observed almost three months after the initial infection with RSV.

Conclusion

Neonatal RSV exposure results in long term pulmonary inflammation and exacerbates allergic airways disease. The early increase in TNF-α in the bronchoalveolar lavage implicates this inflammatory cytokine in orchestrating these events. Finally, the data presented emphasize IL-13 and TNF-α as potential therapeutic targets for treating RSV induced-asthma.     

Surfactant Protein-D Is Essential for Immunity to Helminth Infection

Pulmonary epithelial cell responses can enhance type 2 immunity and contribute to control of nematode infections. An important epithelial product is the collectin Surfactant Protein D (SP-D). We found that SP-D concentrations increased in the lung following Nippostrongylus brasiliensis infection; this increase was dependent on key components of the type 2 immune response. We carried out loss and gain of function studies of SP-D to establish if SP-D was required for optimal immunity to the parasite. N. brasiliensis infection of SP-D-/- mice resulted in profound impairment of host innate immunity and ability to resolve infection. Raising pulmonary SP-D levels prior to infection enhanced parasite expulsion and type 2 immune responses, including increased numbers of IL-13 producing type 2 innate lymphoid cells (ILC2), elevated expression of markers of alternative activation by alveolar macrophages (alvM) and increased production of the type 2 cytokines IL-4 and IL-13. Adoptive transfer of alvM from SP-D-treated parasite infected mice into naïve recipients enhanced immunity to N. brasiliensis. Protection was associated with selective binding by the SP-D carbohydrate recognition domain (CRD) to L4 parasites to enhance their killing by alvM. These findings are the first demonstration that the collectin SP-D is an essential component of host innate immunity to helminths.     

Persistent airway hyperresponsiveness after neonatal viral bronchiolitis in rats.

Viral bronchiolitis in human infants has been associated with permanent changes in small airways and gas exchange and an increased incidence of hyperresponsive airways later in life. Respiratory infection by Sendai virus in neonatal rats also has been reported to cause permanent changes in lung morphology and increased numbers of bronchiolar mast cells and eosinophils. We evaluated pulmonary mechanics, gas exchange, and airway responsiveness in rats at 7 and 13-16 wk after neonatal Sendai virus infection. Rats from the virus group had lower arterial PO2 and increased total lung resistance compared with controls. There were no significant differences between groups for arterial PCO2, dynamic lung compliance, quasi-static respiratory system compliance, or vital capacity. Rats from the infected group were significantly more sensitive to aerosolized methacholine than were controls, although both virus and control groups became less sensitive with age. We conclude that neonatal Sendai virus infection in rats results in persistent alterations in lung function and airway responsiveness. This phenomenon may be valuable for the study of the relationships among airway inflammation, lung morphology, and airway hyperresponsiveness, and it may be relevant to human airway disease.     

IL-33, a potent inducer of adaptive immunity to intestinal nematodes

IL-33 (IL-1F11) binds ST2 (IL-1R4), both of which are associated with optimal CD4(+) Th2 polarization. Exogenous IL-33 drives induction of Th2-associated cytokines and associated pathological changes within the gut mucosa. Th2 polarization is also a prerequisite to expulsion of the intestinal-dwelling nematode Trichuris muris. In this study, we demonstrate that IL-33 mRNA is expressed early during parasite infection and susceptible mice can be induced to expel the parasite by a regime of exogenous IL-33 administration. IL-33 prevents an inappropriate parasite-specific Th1-polarized response and induces IL-4, IL-9, and IL-13. This redirection requires the presence of T cells and must occur at the initiation of the response to the pathogen. Interestingly, exogenous IL-33 also induced thymic stromal lymphopoietin mRNA within the infected caecum, an epithelial cell-restricted cytokine essential for the generation of Th2-driven parasite immunity. IL-33 also acts independently of T cells, altering intestinal pathology in chronically infected SCID mice, leading to an increased crypt length and intestinal epithelial cell proliferation, but reducing goblet cell hyperplasia. Thus, the ability of IL-33 to induce Th2 responses has functional relevance in the context of intestinal helminth infection, particularly during the initiation of the response.     

IL-13-induced airway hyperreactivity during respiratory syncytial virus infection is STAT6 dependent

Airway damage and hyperreactivity induced during respiratory syncytial virus (RSV) infection can have a prolonged effect in infants and young children. These infections can alter the long-term function of the lung and may lead to severe asthma-like responses. In these studies, the role of IL-13 in inducing and maintaining a prolonged airway hyperreactivity response was examined using a mouse model of primary RSV infection. Using this model, there was evidence of significant airway epithelial cell damage and sloughing, along with mucus production. The airway hyperreactivity response was significantly increased by 8 days postinfection, peaked during days 10-12, and began to resolve by day 14. When the local production of Th1- and Th2-associated cytokines was examined, there was a significant increase, primarily in IL-13, as the viral response progressed. Treatment of RSV-infected mice with anti-IL-13 substantially inhibited airway hyperreactivity. Anti-IL-4 treatment had no effect on the RSV-induced responses. Interestingly, when IL-13 was neutralized, an early increase in IL-12 production was observed within the lungs, as was a significantly lower level of viral Ags, suggesting that IL-13 may be regulating an important antiviral pathway. The examination of RSV-induced airway hyperreactivity in STAT6(-/-) mice demonstrated a significant attenuation of the response, similar to the anti-IL-13 treatment. In addition, STAT6(-/-) mice had a significant alteration of mucus-producing cells in the airway. Altogether, these studies suggest that a primary factor leading to chronic RSV-induced airway dysfunction may be the inappropriate production of IL-13.     

Infection of white rat peritoneal macrophages with Toxoplasma gondii, (Coccidia: Sarcocystidae) after Trypanosoma lewisi (Kinetoplastida: Trypanosomatidae) infection

Peritoneal macrophages from Wistar rats, inoculated and non-inoculated with 10(6) T. lewisi trypomastigotes, were cultured and infected with 10(6) T. gondii tachyzoites. Multiplication rates of this parasite were studied after 1, 24 and 48 h of infection but there were not significant differences between the number of parasites found inside of macrophages coming, either from T. lewisi infected or non infected rats. On the other hand, in vivo studies of Toxoplasma multiplication inside peritoneal macrophages, showed that there is an increase of parasite number in cells from T. lewisi infected rats, as compared with those macrophages from non infected rats. This effect was statistically significant and was more evident after four days of infection. Therefore, it has been demonstrated that in vivo, but not in vitro T. lewisi infections, causes an important decrease of the natural resistance to T. gondii of the white rats, which is manifested by the major invasion and multiplication of the parasite inside of peritoneal macrophages.     

Effects of salbutamol and Ro-20-1724 on airway and parenchymal mechanics in rats.

We investigated the effects of a selective beta(2)-agonist, salbutamol, and of phosphodiesterase type 4 inhibition with 4-(3-butoxy-4-methoxy benzyl)-2-imidazolidinone (Ro-20-1724) on the airway and parenchymal mechanics during steady-state constriction induced by MCh administered as an aerosol or intravenously (iv). The wave-tube technique was used to measure the lung input impedance (ZL) between 0.5 and 20 Hz in 31 anesthetized, paralyzed, open-chest adult Brown Norway rats. To separate the airway and parenchymal responses, a model containing an airway resistance (Raw) and inertance (Iaw), and a parenchymal damping (G) and elastance (H), was fitted to ZL spectra under control conditions, during steady-state constriction, and after either salbutamol or Ro-20-1724 delivery. In the Brown Norway rat, the response to iv MCh infusion was seen in Raw and G, whereas continuous aerosolized MCh challenge produced increases in G and H only. Both salbutamol, administered either as an aerosol or iv, and Ro-20-1724 significantly reversed the increases in Raw and G when MCh was administered iv. During the MCh aerosol challenge, Ro-20-1724 significantly reversed the increases in G and H, whereas salbutamol had no effect. These results suggest that, after MCh-induced changes in lung function, salbutamol increases the airway caliber. Ro-20-1724 is effective in reversing the airway narrowings, and it may also decrease the parenchymal constriction.     

Strongyloides venezuelensis infections in mice

The course and intensity of Strongyloides venezuelensis infection as compared with S. ratti infection were investigated in BALB/c mice. The mice were found to be much more susceptible to infection with S. venezuelensis than S. ratti. The majority of worms inoculated were recovered from the lungs and subsequently from the small intestines, suggesting that their migratory route via the lungs to the small intestine was comparable to that of S. stercoralis in humans. Spontaneous expulsion of worms occurred by about 10 days after infection, which was the same as that of S. ratti. Different infectivities, as assessed by faecal egg excretion, age, sex and strain of mouse were observed in mice infected with S. venezuelensis, as well as in those infected with S. ratti. A striking immunity was acquired following a primary exposure to S. venezuelensis. Mice infected with S. venezuelensis are considered to provide as useful a model as those infected with S. ratti for the study of human strongyloidiasis.     

Neospora caninum: infection induced IL-10 overexpression in rat astrocytes in vitro

The effect of Neospora caninum, a parasite that causes abortion and neuromuscular changes, has been investigated on a major population of neural cells, the astrocytes. Highly enriched astroglial primary cultures obtained from neonatal rats were infected after 21 days of culture. Astroglial reactivity, IL-10 and IFN-gamma expression, and cell viability (lactate dehydrogenase activity, metabolization of tetrazolium salt, and trypan blue exclusion assay) have been investigated after 24 and 72 h of infection. Astroglial hypertrophy, gliofilament reorganization, metabolic changes suggesting hypoxia and a strong IL-10 release have been observed in the infected cells. These results show that neural cells are targets for the parasite and that astrocytes may contribute to the CNS immune response to the parasite.     

Respiratory syncytial virus predisposes mice to augmented allergic airway responses via IL-13-mediated mechanisms.

The development of severe childhood asthma may be influenced by several factors including environmental and infectious stimuli. The causal relationship between infectious viral responses, such as respiratory syncytial virus (RSV), and severe asthma during early childhood is unclear. In these studies, the ability for an initial RSV infection to exacerbate and promote a more severe asthmatic-type response was investigated by combining established murine models of disease. We examined the ability of RSV to induce exacerbation of allergic disease over a relatively long period, leading to development of severe airway responses including airway inflammation and hyperreactivity. The preferential production of IL-13 during a primary RSV infection appears to play a critical role for the exacerbation of cockroach allergen-induced disease. The depletion of IL-13 during RSV infections inhibited the exacerbation and acceleration of severe allergen-induced airway hyperreactivity. This was indicated by decreases in airway hyperreactivity and changes in lung chemokine production. These data suggest that the airway responses during asthma can be greatly affected by a previous RSV infection, even when infection occurs before allergen sensitization. Overall, infection of the airways with RSV can induce an IL-13-dependent change in airway function and promotes an environment that contributes to the development of severe allergic asthmatic responses.