Toll-like receptor modulation of murine cerebral malaria is dependent on the genetic background of the host

作者：Griffith Jason W; O'Connor Christine; Bernard Ken; Town Terrence; Goldstein Daniel R; Bucala Richard^*

来源：Journal of Infectious Diseases, 2007, 196(10): 1553-1564.

DOI：10.1086/522865

Infection with Plasmodium berghei ANKA is a well-established model of human cerebral malaria (CM). We show herein that Toll-like receptor (TLR) signaling influences the development of lethal CM in P. berghei ANKA infected mice. Modulation of outcome was dependent on genetic background, such that deletion of myeloid differentiation factor (MyD) 88 on the susceptible C57BL/ 6 background resulted in resistance to CM, whereas deletion of MyD88 on the resistant BALB/ c background led to increased mortality. Our data show that MyD88 influenced the production of T helper-polarizing cytokines, including interferon (IFN)-gamma, interleukin (IL)-4, and IL-17, as well as the total number of Foxp3(+) regulatory T (T-reg) cells in a manner dependent on host genetic background. In addition, mRNA levels of IFN-gamma, CXCL10, and CXCL9 were strongly up-regulated in the brains of susceptible wild-type but not MyD88(-/-) infected mice. These results suggest that TLR signaling and host genetic background influences the pathogenesis of CM via modulation of cytokine production and Treg cell numbers.

• 出版日期2007-11-15