Dynamics of immune granuloma formation in a Leishmania braziliensis-induced self-limiting cutaneous infection in the primate Macaca mulatta.
In order to unravel the physiopathology of leishmaniasis in humans, it is necessary to better understand how Leishmania are able to survive for years within immunologically active granulomas. In the present study, we used a macaque (Macaca mulatta) model of infection with Leishmania braziliensis as a means of assessing the usefulness of this primate system. This model more closely mirrors human protective immunity to Leishmania than the murine model; therefore, we used it to study the host inflammatory granulomatous response involved in the control of cutaneous leishmaniasis. Infected primates developed localized long-term skin ulcerations, but complete spontaneous clinical healing occurred in all infected animals. The infection induced the recruitment and activation of inflammatory mast cells, granulocytes, mononuclear phagocytes, and lymphocytes at the site of infection. During the acute reaction, polymorphonuclear leukocytes were more prominent than other cell types and apparently destroyed many parasites; macrophages then rapidly engulfed dying neutrophils together with their parasitic cargo. In the chronic phase, persisting parasites induced a typical T helper (Th) cytokine, type 1-mediated, immunity-induced granulomatous reaction. By this time, more or less differentiated macrophage accumulations were found, and these evolved to become mature tissue granulomas consisting of all the specific cell types found within human granulomas. In the healing stage, fibroblasts proliferated at the periphery and finally invaded the granulomas with fibrotic substitution. These findings point to the feasibility of using this model to elucidate the potentially disabling Th1-cell mechanisms that may eventually render the host granulomatous response inadequate for fighting L. braziliensis infections.
Souza-Lemos
C
C
Laboratório de Pesquisa em Leishmaniose, Instituto Oswaldo Cruz/Fiocruz, Rio de Janeiro, Brazil.
de-Campos
S N
SN
Teva
A
A
Côrte-Real
S
S
Fonseca
E C
EC
Porrozzi
R
R
Grimaldi
G
G
D000818:Animals; D000953:Antigens, Protozoan / Q000032:analysis; D002634:Chemotaxis, Leukocyte; D005434:Flow Cytometry; D006099:Granuloma / Q000276:immunology / Q000469:parasitology; D016130:Immunophenotyping; D007892:Leishmania braziliensis / Q000502:physiology* / Q000648:ultrastructure; D016773:Leishmaniasis, Cutaneous / Q000276:immunology*; D007958:Leukocyte Count; D008253:Macaca mulatta / Q000276:immunology* / Q000469:parasitology; D008297:Male; D008854:Microscopy, Electron; D023421:Models, Animal; D008992:Monkey Diseases / Q000276:immunology / Q000469:parasitology*; D012867:Skin / Q000276:immunology* / Q000469:parasitology*; D013601:T-Lymphocytes / Q000276:immunology
D000953:Antigens, Protozoan