Viral appropriation of apoptotic and NF-kappaB signaling pathways

Viruses utilize a variety of strategies to evade the host immune response and replicate in the cells they infect. The comparatively large genomes of the Orthopoxviruses and gammaherpesviruses encode several immunomodulatory proteins that are homologous to component of the innate immune system of host cells, which are reviewed here. However, the viral mechanisms used to survive host responses are quite distinct between these two virus families. Poxviruses undergo continuous lytic replication in the host cytoplasm while expressing many genes that inhibit innate immune responses. In contrast, herpesviruses persist in a latent state during much of their lifecycle while expressing only a limited number of relatively non-immunogenic viral proteins, thereby avoiding the adaptive immune response. Poxviruses suppress, whereas latent gammaherpesviruses activate, signaling by NF-kappaB, yet both viruses target similar host signaling pathways to suppress the apoptotic response. Here, modulation of apoptotic and NF-kappaB signal transduction pathways are examined as examples of common pathways appropriated in contrasting ways by herpesviruses and poxviruses.     

Humoral immune response in relation to senescence, sex and sexual ornamentation in the barn swallow (Hirundo rustica)

Performance of animals may decline with age. The effects of senescence, however, may differ between the sexes because of differences in physiology and behaviour. Acquired immunity provides hosts with efficient mechanisms of anti-parasite defence, but the effect of senescence on immunocompetence has never been studied in natural populations. In the barn swallow (Hirundo rustica), primary antibody response to an antigen during one breeding season declined with age in females, while secondary response during the following breeding season declined with age in both sexes. Parasite-mediated sexual selection theory posits that male secondary sexual characters reveal resistance to parasites. Males with large tail ornaments had stronger primary response, retained larger antibody levels until the following year, but did not differ in secondary response compared with short-tailed males, as predicted if ornamentation reflects resistance to parasites. This is the first study showing that immunocompetence declines with age in any vertebrate under natural conditions.     

Do bacterial infections cause reduced ejaculate quality? A meta-analysis of antibiotic treatment of male infertility

Ejaculate quality may limit male reproductive success, and consequently,sperm quality is of importance. Spermatozoa are perceived as"non-self" by the immune system and are exposed to immunologicalattacks in the male reproductive tract. To reduce immunologicalreactions against their own sperm, males are dependent on thetestis being an immunoprivileged site. Immunoprivilege is obtainedby the blood-testis barrier and by local immunosuppression byandrogens. Despite this testicular immunosuppression, an influxof leukocytes may occur in testes. The condition in which maleshave a heightened level of leukocytes in semen is called leukocytospermia,and it is associated with reduced fertility. As the abilityof immunosuppression by androgens may depend on current intensitiesof infectious organisms in the extratesticular soma, only maleswith high parasite resistance may be able to bear the cost ofimmunosuppression and consequently produce high quality ejaculates.This issue is addressed by a meta-analysis on the effects ofbroad-spectrum antibiotic treatment of male leukocytospermia-associatedinfertility. The analysis showed that antibiotic treatment ofleukocytospermic men, without diagnosed genital tract infections,resulted in a significant improvement of ejaculate quality,that is, an increase in ejaculate volume, sperm concentration,number of motile spermatozoa, and number of spermatozoa withnormal morphology. Moreover, the amount of leukocytes in semenwas also reduced. This suggests that broad-spectrum treatmenttargeted toward bacterial infections reduces the density ofleukocytes in semen and, at the same time, improves the qualityof ejaculates produced. Our results emphasize the importanceof parasitic resistance and immunity as factors that cause variationsin ejaculate quality.     

Placental acquisition of maternal specific IgG and Helicobacter pylori colonization in infancy

Background. Colonization with Helicobacter pylori generally occurs in infancy, and the microorganism is often acquired from close family members. Rate of infant colonization may be affected by maternal immune status. Methods. To investigate the potential protective effect of anti‐H. pylori immunoglobulin G (IgG) acquired via the placenta, 65 mothers and their infants were studied from the infant's birth for 1 year. Circulating IgG antibodies were measured by enzyme‐linked immunosorbent assay (ELISA) in cord blood and every 8 weeks. Immunoblotting was performed on sera from infants with significant increases in IgG levels. Rate of infant H. pylori colonization was measured by ¹³C urea breath tests every 4 weeks from the age of 12 weeks. Results. Maternal and infant cord blood specific IgG levels were correlated (R² = .747, p < .001). Infant H. pylori specific IgG fell 5‐fold compared to maternal levels over the first 6 months of life, and rose subsequently in many cases, with the development of novel immunoblot patterns. There were no significant associations between the age at first positive urea breath test and maternal or infant cord specific H. pylori IgG levels. Conclusions. Transplacentally acquired specific IgG antibody does not protect infants from colonization by H. pylori.     

Effect of adult nutrition on the melanization immune response of the malaria vector Anopheles stephensi

Two dietary resources - blood and sugar - were assessed for effects on the melanization immune response of the mosquito Anopheles stephensi Liston (Diptera: Culicidae) towards inoculated Sephadex beads (negatively charged C-25). This melanization is conferred by genetic factors capable of making the mosquito refractory to malaria parasites. If An. stephensi females had obtained a bloodmeal one day before inoculation with a bead, the efficacy of their immune response increased with the concentration of sugar ingested. At the highest sugar concentration (6%) tested, 38% of the mosquitoes completely melanized their bead, whereas at the lowest sugar concentration (2%), none of the mosquitoes were able to melanize their bead completely. Among mosquitoes not having a bloodmeal, the immuno-competence was low (c. 9% of the mosquitoes completely melanized their bead) and independent of sugar concentration. The observed interaction between these two resources indicates that both resources are required for the Anopheles female to develop an effective melanization immune response.     

Antigen delivery to mucosa-associated lymphoid tissues using liposomes as a carrier

Oral vaccination requires an antigen delivery vehicle to protect the antigen and to enhance translocation of the antigen to the mucosa-associated lymphoid tissue. A variety of antigen delivery vehicles including liposomes have been studied for mucosal immunization. The advantages of liposome formulations are their particulate form and the ability to accommodate immunomodulators and targeting molecules in the same package. Many conventional liposomes are variably unstable in acids, pancreatic juice and bile. Nevertheless, carefully designed liposomes have demonstrated an impressive efficacy in inducing mucosal IgA responses, compared to free antigens and other delivery vehicles. However, liposomes as an oral vaccine vehicle are not yet optimized. To design liposomes that are stable in the harsh intestinal environment and are efficiently taken up by the M cells remains a challenge. This review summarizes recent research efforts using liposomes as an antigen carrier for oral vaccines with practical attention to liposome designs and interaction with the M cells.     

Immune expulsion of the trichostrongylid Cooperia oncophora is associated with increased eosinophilia and mucosal IgA

Previous experiments have shown that a primary infection with 100000 infective larvae of the trichostrongylid Cooperia oncophora allows discrimination between different type of responder animals based on the speed by which the parasite is expelled from the host. In most of the animals (intermediate responders) the expulsion occurs 35-42 days after infection. This experiment was carried out to investigate which mechanisms contribute to the clearance of the parasite from the intestine. Sequential necropsy of the animals 14, 28 and 42 days after infection together with a segmental division of the small intestine, allowed us to characterise essential components associated with development of immunity and expulsion of the parasite from its niche. The results show that during the patent phase of the infection the parasite preferentially resides in the proximal gut. Forty-two days after infection ongoing expulsion is characterised by a migration of the worms to the more distal part of the intestine. Expulsion of the adult worm population appears to be mast-cell independent and is associated with a significant increase in parasite-specific mucous IgA and IgG1 as well as with an influx of eosinophils in the intestinal lamina propria. Although we did not observe a specific lymphocyte recruitment into the intestinal mucosa, the accumulation of eosinophils seems to be mediated by CD4+ cells. We measured significant negative correlations between the number of eosinophils and the expulsion rate of the parasite expressed by sex ratio and ratio eggs per gram faeces. Parasite-specific mucosal IgA levels were negatively correlated to the fecundity of the worms, expressed as number of eggs per female worm. Our results describe the involvement of both eosinophils and mucosal IgA in the regulation of C. oncophora expulsion and suggest the development of a Th2 effector immune response.     

Effects of intestinal survival surgery on systemic and mucosal immune responses in SIV-infected rhesus macaques

Abstract: Evaluation of cellular immunity in the intestinal lamina propria of rhesus macaques has been used previously to assess protective immunity against mucosal simian immunodeficiency virus (SIV) challenges. As this technique requires survival surgery to obtain jejunal tissue, effects of surgical stress on the immune system were investigated. SIV-specific immune responses, including IgG and IgA binding antibodies in sera and mucosal secretions, IgG and IgA secreting cells in peripheral blood, IgG neutralizing antibodies, T-cell proliferative responses, and interferon-γ secretion by peripheral blood mononuclear cells, were evaluated pre- and post-surgery in macaques immunized with adenovirus-SIV recombinant vaccines and SIV envelope protein and in SIV-infected macaques. No differences in these immune parameters were observed in SIV-naïve, immunized macaques or healthy SIV-infected macaques with regard to surgery. A dramatic increase in total IgA antibody level following surgery in the rectal secretions of one SIV-infected macaque that was rapidly progressing to AIDS and failed to recover from surgery was attributed to an abscess that developed at the intestinal site. To date, nearly 30 other macaques have undergone the intestinal survival surgery, some on more than one occasion, without experiencing any clinical difficulty. Overall, our results suggest that in healthy macaques, intestinal resection survival surgery can be conducted safely. Further, the method can be used to reliably sample the intestinal mucosa without major or persistent impact on humoral or cellular immune responses.     

A novel antimicrobial function for a ribosomal peptide from rainbow trout skin

An antimicrobial peptide was purified from skin secretions and epithelial cells of rainbow trout by cation exchange and reversed phase chromatography. Partial N-terminal amino acid sequence of the purified peptide revealed 100% identity with the first 11 residues of a 40S ribosomal peptide from medaka fish. Its molecular mass, determined by matrix-associated laser desorption/ionisation mass spectrometry, was found to be 6676.6Da. These results indicate that this antimicrobial peptide is likely to be the 40S ribosomal protein S30. It is active at submicromolar concentrations, with an effective 50% reduction concentration of 0.02-0.04 microM against Planococcus citreus. Thus, in addition to its conventional function in the cell as part of the small ribosomal subunit, this peptide may play a role in protection against intracellular or extracellular pathogens.     

Isolation and characterization of an acetyl group-recognizing agglutinin from the serum of the Indian white shrimp Fenneropenaeus indicus

A natural agglutinin from the serum of the Indian white shrimp Fenneropenaeus (Penaeus) indicus was purified to electrophoretic homogeneity by a single-step affinity chromatography on N-acetylglucosamine-Sepharose 6B. The expression of hemagglutinating (HA) activity of F. indicus agglutinin (FIA) was independent of the presence of divalent cations and insensitive to their chelators. FIA gave a single symmetrical peak in its native form with a molecular mass estimate of 200 kDa on gel filtration in HPLC, and SDS-PAGE under reducing conditions revealed that it is a homo-oligomer of a 27-kDa subunit protein. The pattern of reactivity of FIA against anti-FIA rabbit serum in immunodiffusion and immunoelectrophoretic analysis provided additional evidence for its purity and homogeneity. HA-inhibition studies documented exclusive specificity of FIA for acetyl groups in carbohydrates independently of the presence of these groups at the C-2 or C-5 position and its stereochemical arrangement in the axial or equatorial orientation. The unique ability of FIA to recognize acetyl groups was also explicitly demonstrated with sialo- and asialo-glycoproteins. Strikingly, FIA also interacted equally with amino acids and chemicals containing acetyl groups, thereby unambiguously demonstrating the exquisite specificity of FIA for an acetyl group, irrespective of the presence of this group in carbohydrate or noncarbohydrate ligands. The susceptibility of HA activity of FIA to inhibition by lipopolysaccharides from diverse gram-negative bacteria as well as its ability to selectively agglutinate several bacterial species isolated from infected shrimps implicate a potential role of this humoral agglutinin of F. indicus in the host immunodefense reactions against microbial invaders.