Platelet activating factor receptor-deficient mice present delayed interferon-gamma upregulation and high susceptibility to Leishmania amazonensis infection.
We investigated the role of the platelet activation factor (PAF) receptor (PAFR) in the outcome of infection with Leishmania amazonensis. PAFR deficient (PAFR(-/-)) mice were infected with L. amazonensis and the course of infection was followed. We found that PAFR(-/-) mice in the C57BL/6 background were more susceptible to infection with L. amazonensis than the wild-type controls, as seen both by lesion size and parasite number at the site of infection. Interferon (IFN)-gamma production was delayed in PAFR(-/-) mice, and lower levels of Ccl5 were found in lesions. Expression of nitric oxide synthase-2 mRNA was found impaired in PAFR(-/-) associated with higher levels of arginase-1 mRNA. Moreover, higher levels of antibodies were produced in response to L. amazonensis by PAFR(-/-) mice. We conclude that signaling through the PAFR is essential for the ability of the murine host to control L. amazonensis infection by driving an adequate immune response.
Santiago
Helton C
HC
Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, CP 486, Av. Antonio Carlos 6627, Pampulha, CEP 30161-970 Belo Horizonte, MG, Brazil.
Braga Pires
Maíra Faria
MF
Souza
Daniele G
DG
Roffê
Ester
E
Côrtes
Denise F
DF
Tafuri
Wagner L
WL
Teixeira
Mauro M
MM
Vieira
Leda Q
LQ
D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D001119:Arginase / Q000096:biosynthesis; D054402:Chemokine CCL1; D018946:Chemokine CCL5; D019742:Chemokines, CC / Q000032:analysis; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D015870:Gene Expression; D006651:Histocytochemistry; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000096:biosynthesis*; D016753:Interleukin-10 / Q000032:analysis; D007894:Leishmania mexicana / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D010980:Platelet Membrane Glycoproteins / Q000172:deficiency* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000172:deficiency* / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D015854:Up-Regulation
D000913:Antibodies, Protozoan; C502258:Ccl1 protein, mouse; C503460:Ccl5 protein, mouse; D054402:Chemokine CCL1; D018946:Chemokine CCL5; D019742:Chemokines, CC; D007074:Immunoglobulin G; D010980:Platelet Membrane Glycoproteins; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D014409:Tumor Necrosis Factor-alpha; C039351:platelet activating factor receptor; D016753:Interleukin-10; D007371:Interferon-gamma; D052247:Nitric Oxide Synthase Type II; D001119:Arginase