Macrophage Colony Stimulating Factor Derived from CD4+ T Cells Contributes to Control of a Blood-Borne Infection

PLoS Pathogens

Gabrielly L. de Melo¹  Chioma Anidi¹  Charles C. Kim¹  So Youn Lee¹  Mary F. Fontana¹  Rebecca Hamburger¹  Jennifer Pham¹  Chris Y. Kim¹ 

[1] Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, San Francisco, CA, United States of America

关键词: T cells;    Macrophages;    Parasitic diseases;    Mouse models;    Monocytes;    Parasitemia;    Bone marrow cells;    Lymph nodes;   

DOI  :  10.1371/journal.ppat.1006046

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Dynamic regulation of leukocyte population size and activation state is crucial for an effective immune response. In malaria, Plasmodium parasites elicit robust host expansion of macrophages and monocytes, but the underlying mechanisms remain unclear. Here we show that myeloid expansion during P. chabaudi infection is dependent upon both CD4+ T cells and the cytokine Macrophage Colony Stimulating Factor (MCSF). Single-cell RNA-Seq analysis on antigen-experienced T cells revealed robust expression of Csf1, the gene encoding MCSF, in a sub-population of CD4+ T cells with distinct transcriptional and surface phenotypes. Selective deletion of Csf1 in CD4+ cells during P. chabaudi infection diminished proliferation and activation of certain myeloid subsets, most notably lymph node-resident CD169+ macrophages, and resulted in increased parasite burden and impaired recovery of infected mice. Depletion of CD169+ macrophages during infection also led to increased parasitemia and significant host mortality, confirming a previously unappreciated role for these cells in control of P. chabaudi. This work establishes the CD4+ T cell as a physiologically relevant source of MCSF in vivo; probes the complexity of the CD4+ T cell response during type 1 infection; and delineates a novel mechanism by which T helper cells regulate myeloid cells to limit growth of a blood-borne intracellular pathogen.

【 授权许可】

CC BY