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

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

Research output: Contribution to journalArticle

11 Citations (Scopus)

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

Fingerprint

Ehrlichiosis
Chemokines
Septic Shock
Interleukin-1
Interleukin-10
Ehrlichia chaffeensis
Ehrlichia
Cytokines
Toll-Like Receptor 2
Chemokine CCL5
Lymphopenia
Toll-Like Receptor 4
Interleukin-13
Tumor Necrosis Factor Receptors
Wounds and Injuries
Leukopenia
Immunologic Factors
Granulocyte Colony-Stimulating Factor
Interleukin-8
Cellular Immunity

Keywords

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

ASJC Scopus subject areas

  • Immunology

Cite this

Immune Mediators of protective and pathogenic immune responses in patients with mild and fatal human monocytotropic ehrlichiosis. / Ismail, Nahed; Walker, David; Ghose, Purnima; Tang, Yi Wei.

In: BMC Immunology, Vol. 13, 26, 21.05.2012.

Research output: Contribution to journalArticle

@article{59d213bf4a434d108218713973c36dda,
title = "Immune Mediators of protective and pathogenic immune responses in patients with mild and fatal human monocytotropic ehrlichiosis",
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.",
keywords = "Apoptosis, Chemokines, Cytokines, Death Receptors, Ehrlichiosis, Human ehrlichiosis, Pro-inflammatory cytokines, T cells, Th1 response, Toxic shock",
author = "Nahed Ismail and David Walker and Purnima Ghose and Tang, {Yi Wei}",
year = "2012",
month = "5",
day = "21",
doi = "10.1186/1471-2172-13-26",
language = "English (US)",
volume = "13",
journal = "BMC Immunology",
issn = "1471-2172",
publisher = "BioMed Central",

}

TY - JOUR

T1 - Immune Mediators of protective and pathogenic immune responses in patients with mild and fatal human monocytotropic ehrlichiosis

AU - Ismail, Nahed

AU - Walker, David

AU - Ghose, Purnima

AU - Tang, Yi Wei

PY - 2012/5/21

Y1 - 2012/5/21

N2 - 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.

AB - 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.

KW - Apoptosis

KW - Chemokines

KW - Cytokines

KW - Death Receptors

KW - Ehrlichiosis

KW - Human ehrlichiosis

KW - Pro-inflammatory cytokines

KW - T cells

KW - Th1 response

KW - Toxic shock

UR - http://www.scopus.com/inward/record.url?scp=84861213678&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84861213678&partnerID=8YFLogxK

U2 - 10.1186/1471-2172-13-26

DO - 10.1186/1471-2172-13-26

M3 - Article

C2 - 22607204

AN - SCOPUS:84861213678

VL - 13

JO - BMC Immunology

JF - BMC Immunology

SN - 1471-2172

M1 - 26

ER -