Platelet activating factor receptor-deficient mice present delayed interferon-γ upregulation and high susceptibility to Leishmania amazonensis infection

• Published in: Microbes and infection 2006-09, Vol.8 (11), p.2569-2577
• Main Authors: Santiago, Helton C., Braga Pires, Maíra Faria, Souza, Daniele G., Roffê, Ester, Côrtes, Denise F., Tafuri, Wagner L., Teixeira, Mauro M., Vieira, Leda Q.
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Protozoan - blood; Arginase - biosynthesis; Biological and medical sciences; Chemokine CCL1; Chemokine CCL5; Chemokines, CC - analysis; Cytokines; Disease Models, Animal; Disease Susceptibility; Fundamental and applied biological sciences. Psychology; Gene Expression; Histocytochemistry; Immunoglobulin G - blood; Interferon-gamma - biosynthesis; Interleukin-10 - analysis; Leishmania amazonensis; Leishmania mexicana - immunology; Leishmaniasis, Cutaneous - immunology; Leishmaniasis, Cutaneous - parasitology; Leishmaniasis, Cutaneous - pathology; Lipid mediators; Mice; Mice, Inbred C57BL; Mice, Knockout; Microbiology; Nitric Oxide Synthase Type II - biosynthesis; Parasitic-protozoan; Platelet Membrane Glycoproteins - deficiency; Platelet Membrane Glycoproteins - genetics; Receptors, G-Protein-Coupled - deficiency; Receptors, G-Protein-Coupled - genetics; RNA, Messenger - analysis; RNA, Messenger - genetics; Th1/Th2 cells; Tumor Necrosis Factor-alpha - analysis; Up-Regulation
• ISSN: 1286-4579; 1769-714X
• DOI: 10.1016/j.micinf.2006.06.011

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)-γ 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.