Protective Immunity and Immunopathology in Ehrlichiosis

Nahed Ismail, Aditya Sharma, Lynn Soong, David H. Walker

Research output: Contribution to journalReview articlepeer-review

6 Scopus citations

Abstract

Human monocytic ehrlichiosis, a tick transmitted infection, ranges in severity from apparently subclinical to fatal toxic shock-like disease. Models in immunocompetent mice range from abortive to uniformly lethal infection, depending on the Ehrlichia species, inoculum dose, and inoculation route. Effective immunity is mediated by CD4+ T lymphocytes and gamma interferon. Lethal infection occurs with early overproduction of proinflammatory cytokines and overproduction of TNF alpha and IL-10 by CD8+ T lymphocytes. Furthermore, fatal ehrlichiosis is associated with TLR 9/MyD88 signaling, upregulation of several inflammasome complexes, and secretion of IL-1 beta, IL-1 alpha, and IL-18 by hepatic mononuclear cells, thus suggesting activation of canonical and noncanonical inflammasome pathways, a deleterious role of IL-18, and a protective role of caspase 1. Autophagy promotes ehrlichial infection, whereas MyD88 signaling hinders ehrlichial infection by inhibiting autophagy induction and flux. During infection of hepatocytes by the lethal ehrlichial species, after interferon alpha receptor signaling, the activation of caspase 11 results in the production of inflammasome-dependent IL-1 beta, extracellular secretion of HMGB1, and pyroptosis. HMGB1 has high levels in lethal ehrlichiosis, thereby suggesting a role in toxic shock. Studies of primary bone marrow-derived macrophages infected by highly avirulent or mildly avirulent ehrlichiae have revealed divergent M1 and M2 macrophage polarization associated with the generation of pathogenic CD8 T cells and neutrophils, and excessive inflammation, or with strong expansion of protective Th1 and NKT cells, resolution of inflammation, and clearance of infection, respectively.

Original languageEnglish (US)
Article number21
JournalZoonoses (Ireland)
Volume2
Issue number1
DOIs
StatePublished - 2022
Externally publishedYes

Keywords

  • autophagy
  • Ehrlichia
  • Ehrlichiosis
  • immunity
  • inflammasomes
  • macrophage polarization
  • obligate intracellular bacteria
  • pattern recognition receptors
  • type I interferon

ASJC Scopus subject areas

  • Infectious Diseases
  • veterinary (miscalleneous)

Fingerprint

Dive into the research topics of 'Protective Immunity and Immunopathology in Ehrlichiosis'. Together they form a unique fingerprint.

Cite this