Leishmania pifanoi pathogenesis: selective lack of a local cutaneous response in the absence of circulating antibody.
Recently, a role for B cells in the pathogenesis associated with infection by Leishmania (Leishmania mexicana complex and L. donovani) has been established. In the case of L. mexicana complex parasites (L. mexicana, L. pifanoi, and L. amazonensis), a critical role for immunoglobulin G-mediated mechanisms for the amastigote stage in the host is evident; however, the immunological mechanisms involved remain to be established. In vitro analysis of the kinetics of parasite uptake by macrophages failed to indicate a major effect of antibody opsonization. Given the importance of CD4(+) T cells in the development of disease caused by these parasites, the possibility that the lack of pathogenesis was due to the lack of development of an immune response at the local site (draining lymph node and/or cutaneous site) was explored. Interestingly, the level of CD4(+)-T-cell activation (proliferation and cytokine) in draining lymph nodes from mice lacking circulating antibody (resistant) was found to be comparable to that in nodes from wild-type mice (susceptible) at 2, 5, and 10 weeks postinfection. However, antibody-deficient animals had markedly reduced numbers of monocytes and lymphocytes recruited or retained at the site of cutaneous infection in comparison to wild-type mice, indicating a selective impairment in the local cutaneous immune response. In vitro antigen presentation studies employing tissue-derived (opsonized) amastigotes demonstrated that L. pifanoi-infected FcR(-/-) macrophages, in contrast to comparably infected wild-type cells, failed to activate Leishmania antigen-specific T lymphocytes. These data, taken together, suggest that one possible mechanism for the role of antibody in pathogenesis may be to mediate parasite uptake and regulate the immune response at the local cutaneous site of infection.
Colmenares
María
M
Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Connecticut 06520-8034, USA.
Constant
Stephanie L
SL
Kima
Peter E
PE
McMahon-Pratt
Diane
D
D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D004423:Ear / Q000469:parasitology; D007891:Leishmania / Q000276:immunology / Q000472:pathogenicity*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000469:parasitology; D008198:Lymph Nodes / Q000276:immunology* / Q000469:parasitology; D008213:Lymphocyte Activation; D008264:Macrophages / Q000469:parasitology; D017737:Macrophages, Peritoneal / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D012867:Skin / Q000276:immunology* / Q000469:parasitology
D000913:Antibodies, Protozoan