Pathogenic role of B cells and antibodies in murine Leishmania amazonensis infection.
Leishmania amazonensis infection, occurring predominantly in Central and South America, can manifest itself in several forms, including those of cutaneous and diffuse cutaneous leishmaniasis. The outcome of L. amazonensis infection depends largely on host immune responses to the parasites. While CD4+ T cell activation is a prerequisite for pathogenesis in L. amazonensis-infected mice, the roles of B cells and their antibody production are unclear. In this study, we provide evidence suggesting that B cells and antibodies are involved in disease pathogenesis. We documented a correlation between B cell activation and lesion progress in immunocompetent mice. In the absence of functional B cells and antibodies, JhD mice showed a delayed onset of disease and developed small lesions. Histological examination of these mice revealed a significant reduction in CD4+ and CD8+ T cells, but not in MAC1+ macrophages, at the infection site. In contrast to the wild-type mice that showed typical tissue necrosis, L. amazonensis-infected JhD mice showed no or minimal signs of necrotic foci. A marked reduction in CD4+ T cell proliferation and cytokine (IFN-gamma and IL-10) production in infected JhD mice suggested an involvement of B cells and antibodies in the priming of parasite-specific T cells. This notion was further supported by the observations that adoptive transfer of B cells or antibodies could restore CD4+ T cell activation and migration in infected JhD mice. Moreover, antibody coating of parasites could stimulate dendritic cells to produce high levels of cytokines and increase their ability to prime nai ve CD4+ T cells. Since CD4+ T cells are crucial to disease pathogenesis, this study suggests that B cells and their antibody production enhanced L. amazonensis infection, partially by promoting T cell priming and cellular migration to the infection site.
Wanasen
Nanchaya
N
Department of Microbiology & Immunology, Center for Biodefense and Emerging Infections, University of Texas Medical Branch, Medical Research Building, Room 3.132, 301 University Boulevard, Galveston, TX 77555-1070, USA.
Xin
Lijun
L
Soong
Lynn
L
D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood*; D001402:B-Lymphocytes / Q000276:immunology*; D001938:Brazil; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018920:Coculture Techniques; D016207:Cytokines / Q000097:blood; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006790:Host-Parasite Interactions; D007150:Immunohistochemistry; D007891:Leishmania / Q000502:physiology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology*; D016774:Leishmaniasis, Diffuse Cutaneous / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains
D000913:Antibodies, Protozoan; D016207:Cytokines