Macrophage interactions with neutrophils regulate Leishmania major infection.
Macrophages are host cells for the pathogenic parasite Leishmania major. Neutrophils die and are ingested by macrophages in the tissues. We investigated the role of macrophage interactions with inflammatory neutrophils in control of L. major infection. Coculture of dead exudate neutrophils exacerbated parasite growth in infected macrophages from susceptible BALB, but killed intracellular L. major in resistant B6 mice. Coinjection of dead neutrophils amplified L. major replication in vivo in BALB, but prevented parasite growth in B6 mice. Neutrophil depletion reduced parasite load in infected BALB, but exacerbated infection in B6 mice. Exacerbated growth of L. major required PGE(2) and TGF-beta production by macrophages, while parasite killing depended on neutrophil elastase and TNF-alpha production. These results indicate that macrophage interactions with dead neutrophils play a previously unrecognized role in host responses to L. major infection.
Ribeiro-Gomes
Flávia L
FL
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Otero
Ana C
AC
Gomes
Nitza A
NA
Moniz-De-Souza
Maria Carolina A
MC
Cysne-Finkelstein
Lea
L
Arnholdt
Andrea C
AC
Calich
Vera L
VL
Coutinho
Sergio G
SG
Lopes
Marcela F
MF
DosReis
George A
GA
D000818:Animals; D002450:Cell Communication / Q000276:immunology*; D016923:Cell Death / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis; D004198:Disease Susceptibility; D005260:Female; D005838:Genotype; D007113:Immunity, Innate; D018320:Leishmania major / Q000254:growth & development* / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000235:genetics / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D019272:Leukocyte Elastase / Q000502:physiology; D017737:Macrophages, Peritoneal / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000201:enzymology / Q000276:immunology* / Q000473:pathology / Q000637:transplantation
D016207:Cytokines; D019272:Leukocyte Elastase