ovalbumin and Liver-Diseases--Parasitic

Schistosoma mansoni antigens in the early life alter homologous and heterologous immunity during postnatal infections. We evaluate the immunity to parasite antigens and ovalbumin (OA) in adult mice born/suckled by schistosomotic mothers. Newborns were divided into: born (BIM), suckled (SIM) or born/suckled (BSIM) in schistosomotic mothers, and animals from noninfected mothers (control). When adults, the mice were infected and compared the hepatic granuloma size and cellularity. Some animals were OA + adjuvant immunised. We evaluated hypersensitivity reactions (HR), antibodies levels (IgG1/IgG2a) anti-soluble egg antigen and anti-soluble worm antigen preparation, and anti-OA, cytokine production, and CD4+FoxP3+T-cells by splenocytes. Compared to control group, BIM mice showed a greater quantity of granulomas and collagen deposition, whereas SIM and BSIM presented smaller granulomas. BSIM group exhibited the lowest levels of anti-parasite antibodies. For anti-OA immunity, immediate HR was suppressed in all groups, with greater intensity in SIM mice accompanied of the remarkable level of basal CD4+FoxP3+T-cells. BIM and SIM groups produced less interleukin (IL)-4 and interferon (IFN)-g. In BSIM, there was higher production of IL-10 and IFN-g, but lower levels of IL-4 and CD4+FoxP3+T-cells. Thus, pregnancy in schistosomotic mothers intensified hepatic fibrosis, whereas breastfeeding diminished granulomas in descendants. Separately, pregnancy and breastfeeding could suppress heterologous immunity; however, when combined, the responses could be partially restored in infected descendants.

Topics: Adjuvants, Immunologic; Animals; Animals, Newborn; Animals, Suckling; Antibodies, Helminth; CD4-Positive T-Lymphocytes; Cercaria; Enzyme-Linked Immunosorbent Assay; Female; Flow Cytometry; Forkhead Transcription Factors; Granuloma, Foreign-Body; Immunity, Heterologous; Immunity, Humoral; Immunoglobulin G; Interferon-gamma; Interleukin-10; Interleukin-4; Liver Cirrhosis; Liver Diseases, Parasitic; Male; Mice; Mothers; Ovalbumin; Pregnancy; Schistosoma mansoni; Schistosomiasis mansoni; Spleen

The adenylate cyclase toxoid (ACT) of Bordetella pertussis is capable of delivering its N-terminal catalytic domain into the cytosol of CD11b-expressing professional antigen-presenting cells such as myeloid dendritic cells. This allows delivery of CD8+ T-cell epitopes to the major histocompatibility complex (MHC) class I presentation pathway. Recombinant detoxified ACT containing an epitope of the Plasmodium berghei circumsporozoite protein (CSP), indeed, induced a specific CD8+ T-cell response in immunized mice after a single application, as detected by MHC multimer staining and gamma interferon (IFN-gamma) ELISPOT assay. This CSP-specific response could be significantly enhanced by prime-boost immunization with recombinant ACT in combination with anti-CTLA-4 during the boost immunization. This increased response was accompanied by complete protection in a number of mice after a challenge with P. berghei sporozoites. Transient blockade of CTLA-4 may overcome negative regulation and hence provide a strategy to enhance the efficacy of a vaccine by amplifying the number of responding T cells.

Topics: Adenylate Cyclase Toxin; Animals; Antigens, CD; Antigens, Differentiation; Bordetella pertussis; CD8-Positive T-Lymphocytes; Cells, Cultured; CTLA-4 Antigen; Epitopes, T-Lymphocyte; Female; Forkhead Transcription Factors; Histocompatibility Antigens Class I; Immunization, Secondary; Liver Diseases, Parasitic; Malaria; Malaria Vaccines; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Ovalbumin; Plasmodium berghei; Protozoan Proteins; Protozoan Vaccines; Recombinant Fusion Proteins; T-Lymphocytes, Cytotoxic; T-Lymphocytes, Regulatory