Authors: | Ismail, N.; Walker, D. H.; Ghose, P.; Tang, Y. W. |
Article 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. © 2012 Ismail et al.; licensee BioMed Central Ltd. |
Keywords: | adult; child; controlled study; protein expression; school child; antibiotic therapy; young adult; neutropenia; case report; t cells; interleukin 2; apoptosis; computer assisted tomography; anemia; leukopenia; thrombocytopenia; myalgia; interleukin 10; interleukin 13; interleukin 1beta; interleukin 8; macrophage inflammatory protein 1beta; aciclovir; acute lymphoblastic leukemia; alanine aminotransferase blood level; aspartate aminotransferase blood level; lymphocytopenia; alanine aminotransferase; aspartate aminotransferase; toll like receptor 4; cytokines; disease severity; cellular immunity; immune response; tumor necrosis factor alpha; gamma interferon; blood sampling; receptors, death domain; interleukin 6; cytokine production; thorax radiography; tumor necrosis factor receptor; real time polymerase chain reaction; immunity; th1 cell; urinalysis; monocytes; vancomycin; doxycycline; fatal outcome; levofloxacin; granulocyte colony stimulating factor; toll like receptor 2; monocyte chemotactic protein 1; chemokines; resuscitation; multiple organ failure; natural killer t cell; toll-like receptors; receptors, tumor necrosis factor; cefepime; hypertransaminasemia; septic shock; antigens, cd95; macrophage inflammatory protein 1alpha; pleocytosis; human ehrlichiosis; toxic shock; ehrlichiosis; pro-inflammatory cytokines; death receptors; th1 response; human monocytic ehrlichiosis |
Journal Title: | BMC Immunology |
Volume: | 13 |
ISSN: | 1471-2172 |
Publisher: | Biomed Central Ltd |
Date Published: | 2012-05-21 |
Start Page: | 26 |
Language: | English |
DOI: | 10.1186/1471-2172-13-26 |
PUBMED: | 22607204 |
PROVIDER: | scopus |
PMCID: | PMC3517396 |
DOI/URL: | |
Notes: | --- - "Export Date: 21 May 2013" - "CODEN: BIMMC" - "Source: Scopus" |