Peripheral blood mononuclear cell supernatants from asymptomatic dogs immunized and experimentally challenged with Leishmania chagasi can stimulate canine macrophages to reduce infection in vitro.
Leishmania chagasi is the causative agent of visceral leishmaniasis in both humans and dogs in the New World. The dog is the main domestic reservoir and its infection displays different clinical presentations, from asymptomatic to severe disease. Macrophages play an important role in the control of Leishmania infection. Although it is not an area of intense study, some data suggest a role for canine macrophages in parasite killing by a NO-dependent mechanism. It has been proposed that control of human disease could be possible with the development of an effective vaccine against canine visceral leishmaniasis. Development of a rapid in vitro test to predict animal responses to Leishmania infection or vaccination should be helpful. In this study, an in vitro model was established to test whether peripheral blood mononuclear cell (PBMC) supernatants from dogs immunized with promastigote lysates and infected with L. chagasi promastigotes could stimulate macrophages from healthy dogs in order to control parasite infection. PBMC from a majority of the immunized and experimentally infected dogs expressed IFN-gamma mRNA and secreted IFN-gamma when stimulated with soluble L. chagasi antigen (SLA) in vitro. Additionally, the supernatants from stimulated PBMC were able to reduce the percentage of infected donor macrophages. The results also indicate that parasite killing in this system is dependent on NO, since aminoguanidine (AMG) reversed this effect. This in vitro test appears to be useful for screening animal responses to parasite inoculation as well as studying the lymphocyte effector mechanisms involved in pathogen killing by canine macrophages.
Rodrigues
Cleusa Alves Theodoro
CA
Laboratório de Patologia e Biointervenção, CPqGM, FIOCRUZ/BA, Brazil; Depto. de Morfofisiologia da Universidade Federal de Mato Grosso do Sul, Brazil.
Batista
Luís Fábio da Silva
LF
Teixeira
Márcia Cristina Aquino
MC
Pereira
Andréa Mendes
AM
Santos
Patrícia Oliveira Meira
PO
de Sá Oliveira
Geraldo Gileno
GG
de Freitas
Luiz Antônio Rodrigues
LA
Veras
Patrícia Sampaio Tavares
PS
D000818:Animals; D002478:Cells, Cultured; D004197:Disease Reservoirs / Q000662:veterinary; D004283:Dog Diseases / Q000276:immunology / Q000517:prevention & control*; D004285:Dogs; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism; D007891:Leishmania / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000276:immunology / Q000517:prevention & control / Q000662:veterinary*; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis; D016052:Protozoan Vaccines / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics
D016052:Protozoan Vaccines; D012333:RNA, Messenger; D015847:Interleukin-4; D009569:Nitric Oxide; D007371:Interferon-gamma