title: Platelet activating factor receptor-deficient mice present delayed interferon-gamma upregulation and high susceptibility to Leishmania amazonensis infection.
abstract: 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.
authors.affiliation: 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.
authors.forename: Helton C
authors.initials: HC
authors.lastname: Santiago
authors.forename: Maíra Faria
authors.initials: MF
authors.lastname: Braga Pires
authors.forename: Daniele G
authors.initials: DG
authors.lastname: Souza
authors.forename: Ester
authors.initials: E
authors.lastname: Roffê
authors.forename: Denise F
authors.initials: DF
authors.lastname: Côrtes
authors.forename: Wagner L
authors.initials: WL
authors.lastname: Tafuri
authors.forename: Mauro M
authors.initials: MM
authors.lastname: Teixeira
authors.forename: Leda Q
authors.initials: LQ
authors.lastname: Vieira
mesh_terms: 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
chemical_list: 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