title: Leishmania major induces distinct neutrophil phenotypes in mice that are resistant or susceptible to infection.
abstract: Polymorphonuclear neutrophils (PMN) are key components of the inflammatory response contributing to the development of pathogen-specific immune responses. Following infection with Leishmania major, neutrophils are recruited within hours to the site of parasite inoculation. C57BL/6 mice are resistant to infection, and BALB/c mice are susceptible to infection, developing unhealing, inflammatory lesions. In this report, we investigated the expression of cell surface integrins, TLRs, and the secretion of immunomodulatory cytokines by PMN of both strains of mice, in response to infection with L. major. The parasite was shown to induce CD49d expression in BALB/c-inflammatory PMN, and expression of CD49d remained at basal levels in C57BL/6 PMN. Equally high levels of CD11b were expressed on PMN from both strains. In response to L. major infection, the levels of TLR2, TLR7, and TLR9 mRNA were significantly higher in C57BL/6 than in BALB/c PMN. C57BL/6 PMN secreted biologically active IL-12p70 and IL-10. In contrast, L. major-infected BALB/c PMN transcribed and secreted high levels of IL-12p40 but did not secrete biologically active IL-12p70. Furthermore, IL-12p40 was shown not to associate with IL-23 p19 but formed IL-12p40 homodimers with inhibitory activity. No IL-10 was secreted by BALB/c PMN. Thus, following infection with L. major, in C57BL/6 mice, PMN could constitute one of the earliest sources of IL-12, and in BALB/c mice, secretion of IL-12p40 could contribute to impaired, early IL-12 signaling. These distinct PMN phenotypes may thus influence the development of L. major-specific immune response.
authors: WHO Immunology Research and Training Center, Department of Biochemistry, Epalinges, Switzerland.
authors: Mélanie
authors: M
authors: Charmoy
authors: Rosette
authors: R
authors: Megnekou
authors: Cindy
authors: C
authors: Allenbach
authors: Christine
authors: C
authors: Zweifel
authors: Cynthia
authors: C
authors: Perez
authors: Katia
authors: K
authors: Monnat
authors: Mélanie
authors: M
authors: Breton
authors: Catherine
authors: C
authors: Ronet
authors: Pascal
authors: P
authors: Launois
authors: Fabienne
authors: F
authors: Tacchini-Cottier
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004198:Disease Susceptibility; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000032:analysis / Q000276:immunology; D016753:Interleukin-10 / Q000032:analysis / Q000276:immunology; D053762:Interleukin-12 Subunit p40 / Q000032:analysis / Q000276:immunology; D018320:Leishmania major / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D009573:Nitrites / Q000032:analysis; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D051193:Toll-Like Receptors / Q000276:immunology; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000276:immunology
chemical_list: D053762:Interleukin-12 Subunit p40; D009573:Nitrites; D012333:RNA, Messenger; D051193:Toll-Like Receptors; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D007371:Interferon-gamma