Vaccinia virus infection modulates the hematopoietic cell compartments in the bone marrow.
Successful proliferation and differentiation of hematopoietic progenitor cells in bone marrow (BM) is essential to generate all mature blood cell types, including those involved in the immune response. Although vaccinia virus (VV) is known to induce a strong immune response, the effect of VV infection on hematopoiesis remains largely unknown. Here, we showed that in vivo VV infection results in the expansion of c-Kit(hi)Sca-1+Lin- (KSL) hematopoietic stem cells. The in vivo expansion of the KSL population requires MyD88 that is a critical adaptor for Toll-like receptor-mediated signaling. Moreover, in BM of VV-infected mice, common myeloid progenitors (CMP) was decreased because of the rapid differentiation of CMP to more mature cells. However, the CMP compartment was not affected by VV infection in the absence of MyD88. The common lymphoid progenitor (CLP) cell population was increased regardless of MyD88 status, suggesting the independent regulation of CMP and CLP compartments by VV infection. VV infection also enhanced the potential of progenitors that preferentially induce the programming of dendritic cell (DC) development toward plasmacytoid DC. Therefore, the host immune response is gearing toward antiviral responses as early as at the precursor level upon VV infection.
Singh
Pratibha
P
Department of Microbiology and Immunology and the Walther Oncology Center, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Yao
Yongxue
Y
Weliver
Abigail
A
Broxmeyer
Hal E
HE
Hong
Soon-Cheol
SC
Chang
Cheong-Hee
CH
D000818:Animals; D001853:Bone Marrow / Q000502:physiology / Q000821:virology*; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology / Q000821:virology*; D051379:Mice; D008810:Mice, Inbred C57BL; D053594:Myeloid Differentiation Factor 88 / Q000096:biosynthesis / Q000235:genetics; D014615:Vaccinia / Q000473:pathology / Q000821:virology*; D014616:Vaccinia virus / Q000502:physiology*
C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88