Leishmania majorinduces distinct neutrophil phenotypes in mice that are resistant or susceptible to infection
- 20 April 2007
- journal article
- research article
- Published by Oxford University Press (OUP) in Journal of Leukocyte Biology
- Vol. 82 (2), 288-299
- https://doi.org/10.1189/jlb.0706440
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.Keywords
Funding Information
- The Swiss National Foundation for Scientific Research
This publication has 43 references indexed in Scilit:
- Signal Transduction, Gene Transcription, and Cytokine Production Triggered in Macrophages by Exposure to Trypanosome DNAInfection and Immunity, 2006
- Neutrophils and immunity: challenges and opportunitiesNature Reviews Immunology, 2006
- Hydrogen Peroxide Increases Interleukin‐12 p40/p70 Molecular Ratio and Induces Th2‐Predominant Responses in MiceScandinavian Journal of Immunology, 2006
- New IL-12-family members: IL-23 and IL-27, cytokines with divergent functionsNature Reviews Immunology, 2005
- The expression and roles of Toll-like receptors in the biology of the human neutrophilJournal of Leukocyte Biology, 2005
- Pathological Role of Large Intestinal IL-12p40 for the Induction of Th2-Type Allergic DiarrheaThe American Journal of Pathology, 2004
- Toll-like receptors stimulate human neutrophil functionBlood, 2003
- MyD88 is essential for clearance of Leishmania major: possible role for lipophosphoglycan and Toll‐like receptor 2 signalingEuropean Journal of Immunology, 2003
- Leishmania lipophosphoglycan (LPG) activates NK cells through toll-like receptor-2Molecular and Biochemical Parasitology, 2003
- Interleukin-12 and the regulation of innate resistance and adaptive immunityNature Reviews Immunology, 2003