The biological basis of severe outcomes in Anaplasma phagocytophilum infection

J. Stephen Dumler

Research output: Contribution to journalShort surveypeer-review

Abstract

Anaplasma phagocytophilum causes granulocytic anaplasmosis, an acute disease in humans that is also often subclinical. However, 36% are hospitalized, 7% need intensive care, and the case fatality rate is 0.6%. The biological basis for severe disease is not understood. Despite A. phagocytophilum's mechanisms to subvert neutrophil antimicrobial responses, whether these mechanisms lead to disease is unclear. In animals, inflammatory lesions track with IFNγ and IL-10 expression and infection of Ifng -/- mice leads to increased pathogen load but inhibition of inflammation. Suppression of STAT signaling in horses impacts IL-10 and IFN-γ expression, and also suppresses disease severity. Similar inhibition of inflammation with infection of NKT-deficient mice suggests that innate immune responses are key for disease. With severe disease, tissues can demonstrate hemophagocytosis, and measures of macrophage activation/hemophagocytic syndromes (MAS/HPS) support the concept of human granulocytic anaplasmosis as an immunopathologic disease. MAS/HPS are related to defective cytotoxic lymphocytes that ordinarily diminish inflammation. Pilot studies in mice show cytotoxic lymphocyte activation with A. phagocytophilum infection, yet suppression of cytotoxic responses from both NKT and CD8 cells, consistent with the development of MAS/HPS. Whether severity relates to microbial factors or genetically determined diversity in human immune and inflammatory response needs more investigation.

Original languageEnglish (US)
Pages (from-to)13-20
Number of pages8
JournalFEMS Immunology and Medical Microbiology
Volume64
Issue number1
DOIs
StatePublished - Feb 2012

Keywords

  • Anaplasma
  • Cytotoxic lymphocyte
  • Hemophagocytic syndrome
  • Immunopathology
  • Macrophage activation syndrome
  • Rickettsia

ASJC Scopus subject areas

  • Immunology and Allergy
  • Microbiology
  • Immunology
  • Microbiology (medical)
  • Infectious Diseases

Fingerprint

Dive into the research topics of 'The biological basis of severe outcomes in Anaplasma phagocytophilum infection'. Together they form a unique fingerprint.

Cite this