The PGE2/IL-10 Axis Determines Susceptibility of B-1 Cell-Derived Phagocytes (B-1CDP) to Leishmania major Infection.
B-1 cells can be differentiated from B-2 cells because they are predominantly located in the peritoneal and pleural cavities and have distinct phenotypic patterns and activation properties. A mononuclear phagocyte derived from B-1 cells (B-1CDP) has been described. As the B-1CDP cells migrate to inflammatory/infectious sites and exhibit phagocytic capacity, the microbicidal ability of these cells was investigated using the Leishmania major infection model in vitro. The data obtained in this study demonstrate that B-1CDP cells are more susceptible to infection than peritoneal macrophages, since B-1CDP cells have a higher number of intracellular amastigotes forms and consequently release a larger number of promastigotes. Exacerbated infection by L. major required lipid bodies/PGE2 and IL-10 by B-1CDP cells. Both infection and the production of IL-10 were decreased when PGE2 production was blocked by NSAIDs. The involvement of IL-10 in this mechanism was confirmed, since B-1CDP cells from IL-10 KO mice are more competent to control L. major infection than cells from wild type mice. These findings further characterize the B-1CDP cells as an important mononuclear phagocyte that plays a previously unrecognized role in host responses to L. major infection, most likely via PGE2-driven production of IL-10.
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Angélica F
AF
Arcanjo
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; Departamento de Veterinária, Universidade Federal Rural do Rio de Janeiro, Rio de Janeiro, Brazil.
Isabel F
IF
LaRocque-de-Freitas
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Juliana Dutra B
JD
Rocha
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Daniel
D
Zamith
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Ana Caroline
AC
Costa-da-Silva
Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil.
Marise Pinheiro
MP
Nunes
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Fabio P
FP
Mesquita-Santos
Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Alexandre
A
Morrot
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Alessandra A
AA
Filardy
Departmento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo, São Paulo, Brazil.
Mario
M
Mariano
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Christianne
C
Bandeira-Melo
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
George A
GA
DosReis
Departamento de Veterinária, Universidade Federal Rural do Rio de Janeiro, Rio de Janeiro, Brazil.
Debora
D
Decote-Ricardo
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Célio Geraldo
CG
Freire-de-Lima
D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000469:parasitology*; D015232:Dinoprostone / Q000378:metabolism*; D004198:Disease Susceptibility; D016753:Interleukin-10 / Q000096:biosynthesis / Q000378:metabolism*; D018320:Leishmania major / Q000187:drug effects / Q000254:growth & development / Q000276:immunology / Q000502:physiology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology / Q000469:parasitology*; D066292:Lipid Droplets / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000469:parasitology; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018512:Parasitemia / Q000276:immunology / Q000469:parasitology; D010586:Phagocytes / Q000187:drug effects / Q000469:parasitology*; D010641:Phenotype; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism
D016753:Interleukin-10; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D001241:Aspirin