title: Neutrophils and macrophages cooperate in host resistance against Leishmania braziliensis infection.
abstract: Neutrophils play an active role in the control of infections caused by intracellular pathogens such as Leishmania. In the present study, we investigated the effect of neutrophil depletion at the time of Leishmania braziliensis infection of BALB/c mice and how neutrophils interact with the infected macrophage to promote parasite elimination. The in vivo depletion of neutrophils led to a significant increase in parasite load and enhanced the Th1-Th2 immune response in this experimental model of infection. BALB/c mice coinoculated with both parasites and live neutrophils displayed lower parasite burdens at the site of infection and in the draining lymph nodes. In vitro, we observed that live neutrophils significantly reduced the parasite load in L. braziliensis-infected murine macrophages, an effect not observed with Leishmania major. L. braziliensis elimination was dependent on the interaction between neutrophils and macrophages and was associated with TNF-alpha as well as superoxide production. Furthermore, cooperation between neutrophils and macrophages toward parasite elimination was also observed in experiments performed with L. braziliensis-infected human cells and, importantly, with two other New World Leishmania species. These results indicate that neutrophils play an important and previously unappreciated role in L. braziliensis infection, favoring the induction of a protective immune response.
authors.affiliation: Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Brazil.
authors.forename: Fernanda O
authors.initials: FO
authors.lastname: Novais
authors.forename: Rômulo C
authors.initials: RC
authors.lastname: Santiago
authors.forename: André
authors.initials: A
authors.lastname: Báfica
authors.forename: Ricardo
authors.initials: R
authors.lastname: Khouri
authors.forename: Lilian
authors.initials: L
authors.lastname: Afonso
authors.forename: Valéria M
authors.initials: VM
authors.lastname: Borges
authors.forename: Cláudia
authors.initials: C
authors.lastname: Brodskyn
authors.forename: Manoel
authors.initials: M
authors.lastname: Barral-Netto
authors.forename: Aldina
authors.initials: A
authors.lastname: Barral
authors.forename: Camila I
authors.initials: CI
authors.lastname: de Oliveira
mesh_terms: D000818:Animals; D002450:Cell Communication / Q000276:immunology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D005260:Female; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D007892:Leishmania braziliensis / Q000254:growth & development / Q000276:immunology*; D016774:Leishmaniasis, Diffuse Cutaneous / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D017737:Macrophages, Peritoneal / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020556:Neutrophil Infiltration / Q000276:immunology; D009504:Neutrophils / Q000276:immunology* / Q000469:parasitology / Q000637:transplantation