Immune Mediators of protective and pathogenic immune responses in patients with mild and fatal human monocytotropic ehrlichiosis

Nahed Ismail, David H. Walker, Purnima Ghose, Yi Wei Tang

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Background: Ehrlichia chaffeensis is a bacterial pathogen that causes fatal human monocytic ehrlichiosis (HME) that mimic toxic shock-like syndrome. Murine studies indicate that over activation of cellular immunity followed by immune suppression plays a central role in mediating tissue injury and organ failure during fatal HME. However, there are no human studies that examine the correlates of resistance or susceptibility to severe and fatal HME.Results: In this study, we compared the immune responses in two patients with mild/non fatal and severe/fatal HME who had marked lymphopenia, thrombocytopenia and elevated liver enzymes. The levels of different immunological factors in the blood of those patients were examined and compared to healthy controls. Our data showed that fatal HME is associated with defective production of Th1 cytokines such as ( IFNγ and IL-2), increased anti-inflammatory (IL-10 and IL-13) and pro-inflammatory (TNF-α, IL-1α, IL-1β, and IL-6) cytokines, increased levels of macrophages, T cells, and NK cells chemokines such as MCP-1, MIP-1α, MIP-1β, but not RANTES and IP-10, increased levels of neutrophils chemokine and growth factor (IL-8 and G-CSF), and elevated expression of tumor necrosis factor receptor (TNFR), and toll like receptors 2 and 4 compared to patients with non fatal HME and healthy controls.Conclusions: Fatal Ehrlichia-induced toxic shock is associated with defective Th1 responses, possible immune suppression mediated by IL-10. In addition, marked leukopenia observed in patients with fatal disease could be attributed to enhanced apoptosis of leukocytes and/or elevated chemokine production that could promote migration of immune cells to sites of infection causing tissue injury.

Original languageEnglish (US)
Article number26
JournalBMC Immunology
Volume13
DOIs
StatePublished - May 21 2012

Keywords

  • Apoptosis
  • Chemokines
  • Cytokines
  • Death Receptors
  • Ehrlichiosis
  • Human ehrlichiosis
  • Pro-inflammatory cytokines
  • T cells
  • Th1 response
  • Toxic shock

ASJC Scopus subject areas

  • Immunology

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