MyD88 mediates instructive signaling in dendritic cells and protective inflammatory response during rickettsial infection

Jeremy Bechelli, Claire Smalley, Xuemei Zhao, Barbara Judy, Patricia Valdes, David Walker, Rong Fang

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Spotted fever group rickettsiae cause potentially life-threatening infections throughout the world. Several members of the Tolllike receptor (TLR) family are involved in host response to rickettsiae, and yet the mechanisms by which these TLRs mediate host immunity remain incompletely understood. In the present study, we found that host susceptibility of MyD88-/- mice to infection with Rickettsia conorii or Rickettsia australis was significantly greater than in wild-type (WT) mice, in association with severely impaired bacterial clearance in vivo. R. australis-infected MyD88-/- mice showed significantly lower expression levels of gamma interferon (IFN-γ), interleukin-6 (IL-6), and IL-1β, accompanied by significantly fewer inflammatory infiltrates of macrophages and neutrophils in infected tissues, than WT mice. The serum levels of IFN-γ, IL-12, IL-6, and granulocyte colonystimulating factor were significantly reduced, while monocyte chemoattractant protein 1, macrophage inflammatory protein 1α, and RANTES were significantly increased in infected MyD88-/- mice compared to WT mice. Strikingly, R. australis infection was incapable of promoting increased expression of MHC-IIhigh and production of IL-12p40 in MyD88-/- bone marrow-derived dendritic cells (BMDCs) compared to WT BMDCs, although costimulatory molecules were upregulated in both types of BMDCs. Furthermore, the secretion levels of IL-1β by Rickettsia-infected BMDCs and in the sera of infected mice were significantly reduced in MyD88-/- mice compared to WT controls, suggesting that in vitro and in vivo production of IL-1β is MyD88 dependent. Taken together, our results suggest that MyD88 signaling mediates instructive signals in DCs and secretion of IL-1β and type 1 immune cytokines, which may account for the protective inflammatory response during rickettsial infection.

Original languageEnglish (US)
Pages (from-to)883-893
Number of pages11
JournalInfection and Immunity
Volume84
Issue number4
DOIs
StatePublished - Apr 1 2016

Fingerprint

Dendritic Cells
Rickettsia
Infection
Interleukin-1
Bone Marrow
Interleukin-6
Rickettsia conorii
Interleukin-12 Subunit p40
Macrophage Inflammatory Proteins
Chemokine CCL5
Chemokine CCL2
Interleukin-12
Serum
Granulocytes
Interferons
Interferon-gamma
Immunity
Neutrophils
Fever
Macrophages

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Parasitology
  • Infectious Diseases

Cite this

MyD88 mediates instructive signaling in dendritic cells and protective inflammatory response during rickettsial infection. / Bechelli, Jeremy; Smalley, Claire; Zhao, Xuemei; Judy, Barbara; Valdes, Patricia; Walker, David; Fang, Rong.

In: Infection and Immunity, Vol. 84, No. 4, 01.04.2016, p. 883-893.

Research output: Contribution to journalArticle

Bechelli, Jeremy ; Smalley, Claire ; Zhao, Xuemei ; Judy, Barbara ; Valdes, Patricia ; Walker, David ; Fang, Rong. / MyD88 mediates instructive signaling in dendritic cells and protective inflammatory response during rickettsial infection. In: Infection and Immunity. 2016 ; Vol. 84, No. 4. pp. 883-893.
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