title: Macrophage Colony Stimulating Factor Derived from CD4+ T Cells Contributes to Control of a Blood-Borne Infection.
abstract: 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.
authors.affiliation: Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, San Francisco, CA, United States of America.
authors.forename: Mary F
authors.identifier: http://orcid.org/0000-0003-3630-181X
authors.initials: MF
authors.lastname: Fontana
authors.affiliation: Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, San Francisco, CA, United States of America.
authors.forename: Gabrielly L
authors.initials: GL
authors.lastname: de Melo
authors.affiliation: Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, San Francisco, CA, United States of America.
authors.forename: Chioma
authors.initials: C
authors.lastname: Anidi
authors.affiliation: Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, San Francisco, CA, United States of America.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Hamburger
authors.affiliation: Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, San Francisco, CA, United States of America.
authors.forename: Chris Y
authors.identifier: http://orcid.org/0000-0002-6020-0560
authors.initials: CY
authors.lastname: Kim
authors.affiliation: Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, San Francisco, CA, United States of America.
authors.forename: So Youn
authors.identifier: http://orcid.org/0000-0001-8395-3365
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, San Francisco, CA, United States of America.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Pham
authors.affiliation: Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, San Francisco, CA, United States of America.
authors.forename: Charles C
authors.identifier: http://orcid.org/0000-0001-6474-8227
authors.initials: CC
authors.lastname: Kim
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D016173:Macrophage Colony-Stimulating Factor / Q000096:biosynthesis* / Q000276:immunology*; D008288:Malaria / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D016788:Plasmodium chabaudi / Q000276:immunology; D016133:Polymerase Chain Reaction
chemical_list: D016173:Macrophage Colony-Stimulating Factor