Chronic Trichuris muris infection alters hematopoiesis and causes IFN-γ-expressing T-cell accumulation in the mouse bone marrow.
Proinflammatory cytokines produced during immune responses to infectious stimuli are well-characterized to have secondary effects on the function of hematopoietic progenitor cells in the BM. However, these effects on the BM are poorly characterized during chronic infection with intestinal helminth parasites. In this study, we use the Trichuris muris model of infection and show that Th1 cell-associated, but not acute Th2 cell-associated, responses to chronic T. muris infection cause a major, transient expansion of CD48-CD150-multipotent progenitor cells in the BM that is dependent on the presence of adaptive immune cells and IFN-γ signaling. Chronic T. muris infection also broadly stimulated proliferation of BM progenitor cells including CD48-CD150+hematopoietic stem cells. This shift in progenitor activity during chronic T. muris infection correlated with a functional increase in myeloid colony formation in vitro as well as neutrophilia in the BM and peripheral blood. In parallel, we observed an accumulation of CD4+, CD8+, and CD4-CD8-(double negative) T cells that expressed IFN-γ, displaying activated and central memory-type phenotypes in the bone marrow during chronic infection. Thus, these results demonstrate that Th1 cell-driven responses in the intestine during chronic helminth infection potently influence upstream hematopoietic processes in the BM via IFN-γ.
The Biomedical Research Centre, University of British Columbia, Vancouver, Canada.
Alistair L
AL
Chenery
The Biomedical Research Centre, University of British Columbia, Vancouver, Canada.
Frann
F
Antignano
The Biomedical Research Centre, University of British Columbia, Vancouver, Canada.
Michael R
MR
Hughes
The Biomedical Research Centre, University of British Columbia, Vancouver, Canada.
Kyle
K
Burrows
The Biomedical Research Centre, University of British Columbia, Vancouver, Canada.
Kelly M
KM
McNagny
The Biomedical Research Centre, University of British Columbia, Vancouver, Canada. colby.zaph@monash.edu.|Infection and Immunity Program, Monash Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia. colby.zaph@monash.edu.|Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria, Australia. colby.zaph@monash.edu.
Colby
C
Zaph
D000818:Animals; D001853:Bone Marrow / Q000276:immunology*; D002908:Chronic Disease; D004195:Disease Models, Animal; D006410:Hematopoiesis / Q000276:immunology*; D006412:Hematopoietic Stem Cells / Q000502:physiology; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D007422:Intestines / Q000276:immunology; D051379:Mice; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D014257:Trichuriasis / Q000097:blood* / Q000276:immunology* / Q000469:parasitology; D014258:Trichuris / Q000276:immunology / Q000502:physiology
D007371:Interferon-gamma
Bone marrow; HSC; Hematopoiesis; IFN-γ; T cells; Trichuris muris