ovalbumin and Helminthiasis

The immune response against helminths and allergens is generally characterized by high levels of IgE and increased numbers of Th2 cells, eosinophils, and basophils. Basophils represent a relatively rare population of effector cells and their in vivo functions are incompletely understood. Recent studies with basophil-depleting antibodies revealed that these cells might play an important role during the early and late stages of type 2 immune responses. To further characterize the relevance of basophils for protective immunity and orchestration of allergic inflammation, we generated constitutively basophil-deficient mice. We observed a normal Th2 response induced by helminth infections or immunization with alum/OVA or papain/OVA. However, basophils contributed to worm expulsion during secondary helminth infection and mediated an IgE-dependent inflammatory response of the skin. These results argue against a critical role of basophils as antigen-presenting cells for induction of Th2 polarization and highlight their effector cell potential during later stages of a type 2 immune response.

Topics: Adaptive Immunity; Allergens; Animals; Basophils; Cytotoxicity, Immunologic; Helminthiasis; Humans; Hypersensitivity; Immunity, Innate; Immunoglobulin E; Inflammation; Mice; Mice, Transgenic; Ovalbumin; Th2 Cells

Topics: Animals; Graft vs Host Disease; Helminthiasis; Humans; Hypersensitivity, Immediate; Immunoglobulin E; Immunoglobulin G; In Vitro Techniques; Interleukin-4; Ovalbumin

The impact of endemic parasitic infection on vaccine efficacy is an important consideration for vaccine development and deployment. We have examined whether intestinal infection with the natural murine helminth Heligmosomoides polygyrus bakeri alters Ag-specific Ab and cellular immune responses to oral and parenteral vaccination in mice. Oral vaccination of mice with a clinically relevant, live, attenuated, recombinant Salmonella vaccine expressing chicken egg OVA (Salmonella-OVA) induced the accumulation of activated, OVA-specific T effector cells rather than OVA-specific regulatory T cells in the GALT. Intestinal helminth infection significantly reduced Th1-skewed Ab responses to oral vaccination with Salmonella-OVA. Activated, adoptively transferred, OVA-specific CD4+ T cells accumulated in draining mesenteric lymph nodes of vaccinated mice, regardless of their helminth infection status. However, helminth infection increased the frequencies of adoptively transferred OVA-specific CD4+ T cells producing IL-4 and IL-10 in the mesenteric lymph node. Ab responses to the oral Salmonella-OVA vaccine were reduced in helminth-free mice adoptively transferred with OVA-specific CD4+ T cells harvested from mice with intestinal helminth infection. Intestinal helminth infection also significantly reduced Th2-skewed Ab responses to parenteral vaccination with OVA adsorbed to alum. These findings suggest that vaccine-specific CD4+ T cells induced in the context of helminth infection retain durable immunomodulatory properties and may promote blunted Ab responses to vaccination. They also underscore the potential need to treat parasitic infection before mass vaccination campaigns in helminth-endemic areas.

Topics: Animals; CD4-Positive T-Lymphocytes; Helminthiasis; Intestinal Diseases, Parasitic; Mice; Mice, Inbred BALB C; Ovalbumin; Vaccine Efficacy; Vaccines, Synthetic

The transcription factor promyelocytic leukemia zinc finger (PLZF) is transiently expressed during development of type 2 innate lymphoid cells (ILC2s) but is not present at the mature stage. We hypothesized that PLZF-deficient ILC2s have functional defects in the innate allergic response and represent a tool for studying innate immunity in a mouse with a functional adaptive immune response.. We determined the consequences of PLZF deficiency on ILC2 function in response to innate and adaptive immune stimuli by using PLZF(-/-) mice and mixed wild-type:PLZF(-/-) bone marrow chimeras.. PLZF(-/-) mice, wild-type littermates, or mixed bone marrow chimeras were treated with the protease allergen papain or the cytokines IL-25 and IL-33 or infected with the helminth Nippostrongylus brasiliensis to induce innate type 2 allergic responses. Mice were sensitized with intraperitoneal ovalbumin-alum, followed by intranasal challenge with ovalbumin alone, to induce adaptive TH2 responses. Lungs were analyzed for immune cell subsets, and alveolar lavage fluid was analyzed for ILC2-derived cytokines. In addition, ILC2s were stimulated ex vivo for their capacity to release type 2 cytokines.. PLZF-deficient lung ILC2s exhibit a cell-intrinsic defect in the secretion of IL-5 and IL-13 in response to innate stimuli, resulting in defective recruitment of eosinophils and goblet cell hyperplasia. In contrast, the adaptive allergic inflammatory response to ovalbumin and alum was unimpaired.. PLZF expression at the innate lymphoid cell precursor stage has a long-range effect on the functional properties of mature ILC2s and highlights the importance of these cells for innate allergic responses in otherwise immunocompetent mice.

Topics: Adaptive Immunity; Adoptive Transfer; Allergens; Animals; Antigens, Surface; Biomarkers; Bone Marrow Transplantation; Bronchoalveolar Lavage Fluid; Cytokines; Disease Models, Animal; Helminthiasis; Helminths; Hypersensitivity; Immunity, Innate; Immunophenotyping; Interleukin-33; Interleukins; Kruppel-Like Transcription Factors; Lymphocyte Activation; Lymphocyte Subsets; Mice; Mice, Knockout; Ovalbumin; Papain; Promyelocytic Leukemia Zinc Finger Protein; Pulmonary Eosinophilia; Th2 Cells

Efficacious adjuvants are important components of new vaccines. The neisserial outer membrane protein, PorB, is a TLR2 ligand with unique adjuvant activity. We demonstrate that PorB promotes Th2-skewed cellular immune response to the model Ag, OVA, in mice, including Ag-specific recall eosinophil recruitment to the peritoneum. PorB induces chemokine secretion by myeloid cells using both TLR2-dependent and -independent mechanisms, suggesting that anatomical distribution of TLR2(+) cells may not be a limiting factor for potential vaccine strategies. The results from this study suggest that PorB, and other TLR2 ligands, may be ideal for use against pathogens where eosinophilia may be protective, such as parasitic helminths.

Topics: Adjuvants, Immunologic; Animals; Antigens; Chemokines; Eosinophilia; Eosinophils; Helminthiasis; Helminths; Ligands; Macrophages, Peritoneal; Mast Cells; Mice; Mice, Knockout; Myeloid Cells; Ovalbumin; Porins; Toll-Like Receptor 2; Toll-Like Receptor 4; Vaccines

We have previously found that co-immunisation with ovalbumin (OVA) and the body fluid of the helminth Ascaris suum inhibited an OVA-specific delayed type hypersensitivity (DTH) response by reducing OVA-specific CD4+ T lymphocyte proliferation via an IL-4 independent mechanism. In the present study, we determined whether parasite infections themselves could induce similar changes to peripheral immunisation by examining the modulation of OVA-specific immune responses during acute and chronic helminth infections. Surprisingly, an acute infection with Trichinella spiralis, but not a chronic infection with Heligmosomoides polygyrus, inhibited the OVA-specific DTH reaction. Correspondingly, the T helper 1 (Th1) OVA-specific response was decreased in mice infected with T. spiralis, but not with H. polygyrus. Inhibition of the Th1 response may be a result of a shift in the Th1/Th2 balance as although both H. polygyrus and T. spiralis infected mice induced a Th2 OVA-specific response, that exhibited by T. spiralis was more potent. Furthermore, although IL-10 secretion upon OVA restimulation was similarly increased by both infections, production of this immunoregulatory cytokine may play a role in the suppression of immune responses observed with T. spiralis infection depending on the context of its release. Interestingly, analysis of the OVA-specific T lymphocyte division by carboxyfluorescein diacetate succinimidyl ester (CFSE) staining revealed that gastro-intestinal infection with the acute helminth T. spiralis, but not with chronic H. polygyrus, inhibited the systemic immune response by significantly inhibiting the antigen-specific T cell proliferation during the primary response, a mechanism similar to that observed when A. suum parasite extracts were directly mixed with the OVA during immunisation in our previous studies.

Topics: Acute Disease; Adoptive Transfer; Animals; Antigens, Helminth; CD4 Lymphocyte Count; Chronic Disease; Female; Helminthiasis; Hypersensitivity, Delayed; Immune Tolerance; Intestinal Diseases, Parasitic; Mice; Mice, Transgenic; Models, Animal; Nematospiroides dubius; Ovalbumin; Strongylida Infections; Th1 Cells; Th2 Cells; Trichinella spiralis; Trichinellosis

Topics: Animals; Cell Separation; Cestode Infections; Eosinophilia; Eosinophils; Helminthiasis; Immunization; Mesocestoides; Mice; Mice, Inbred BALB C; Nippostrongylus; Ovalbumin; Peritoneal Cavity

Humoral responses to ovalbumin (OA) administered i.p. with Al(OH)3 were depressed in C57BL mice immunized 5-13 days after infection with N. dubius, but not N. brasiliensis or T. muris. These two parasites induced elevated IgM responses, possibly as a result of systemic contact with parasite larvae or debris since i.v. administered N. dubius also increased IgM titres to OA. Depression of anti-OA IgG titres by N. dubius was also observed in infected BALB/c and CBA mice given OA-Al(OH)3 (i.p.), but not in C57BL mice given OA-Al(OH)3 (s.c.), OA-FCA (i.p. or s.c.), or OA-B, pertussis (i.p.). These findings suggest that local effects of N. dubius within the peritoneum reduce the adjuvanticity of Al(OH)3, resulting in depressed responses to OA-Al(OH)3.

Topics: Animals; Antibody Formation; Enzyme-Linked Immunosorbent Assay; Helminthiasis; Immunoglobulin G; Immunoglobulin M; In Vitro Techniques; Intestinal Diseases; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred CBA; Ovalbumin; Species Specificity

Topics: Animals; Antibodies, Anti-Idiotypic; Antibody Formation; Antigen-Antibody Reactions; Fasciola hepatica; Goats; Helminthiasis; Immunization; Immunization, Secondary; Immunoglobulin E; Ovalbumin; Rats; Species Specificity

Topics: Ancylostomatoidea; Animals; Antibody Formation; Dust; Fasciola hepatica; Fascioliasis; Helminthiasis; Hemocyanins; Hookworm Infections; Immunoglobulin E; Ovalbumin; Rats