Divergent roles for Ly6C+CCR2+CX3CR1+ inflammatory monocytes during primary or secondary infection of the skin with the intra-phagosomal pathogen Leishmania major

PLoS Pathogens

Nicole A. Doria¹  Ehud Inbar¹  Jonatan Mendez¹  David L. Sacks¹  Sang Hun Lee¹  Andrea Paun¹  Eric H. Roma¹  Audrey Romano¹  Flavia L. Ribeiro-Gomes¹  Nathan C. Peters²  Matheus B. H. Carneiro² 

[1] Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States;Snyder Institute for Chronic Diseases, Departments of Microbiology Immunology and Infectious Diseases, Cumming School of Medicine, and Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary, AB, Canada

关键词: Monocytes;    Parasitic diseases;    Inflammation;    Ears;    Neutrophils;    Ear infections;    Respiratory infections;    Parasite replication;   

DOI  :  10.1371/journal.ppat.1006479

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Inflammatory monocytes can be manipulated by environmental cues to perform multiple functions. To define the role of monocytes during primary or secondary infection with an intra-phagosomal pathogen we employed Leishmania major-red fluorescent protein (RFP) parasites and multi-color flow cytometry to define and enumerate infected and uninfected inflammatory cells in the skin. During primary infection, infected monocytes had altered maturation and were the initial mononuclear host cell for parasite replication. In contrast, at a distal site of secondary infection in mice with a healed but persistent primary infection, this same population rapidly produced inducible nitric oxide synthase (iNOS) in an IFN-γ dependent manner and was critical for parasite killing. Maturation to a dendritic cell-like phenotype was not required for monocyte iNOS-production, and enhanced monocyte recruitment correlated with IFN-γ dependent cxcl10 expression. In contrast, neutrophils appeared to be a safe haven for parasites in both primary and secondary sites. Thus, inflammatory monocytes play divergent roles during primary versus secondary infection with an intra-phagosomal pathogen.

【 授权许可】

CC BY