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Title: Pronounced susceptibility to infection by Salmonella enterica serovar Typhimurium in mice chronically exposed to lead correlates with a shift to Th2-type immune responses

Abstract

Persistent exposure to inorganic lead (Pb) is known to adversely affect the immune system. In the present study, we assessed the effect of chronic Pb exposure on susceptibility to infection by the facultative intracellular pathogen Salmonella enterica serovar Typhimurium. Mice were exposed to 10 mM Pb-acetate in drinking water for {approx} 16 weeks, resulting in a significant level of Pb in the blood (106.2 {+-} 8.9 {mu}g/dl). Pb exposure rendered mice susceptible to Salmonella infection, manifested by increased bacterial burden in target organs and heightened mortality. Flow cytometric analysis of the splenic cellular composition in normal and Pb-exposed mice revealed no gross alteration in the ratios of B and T lymphocytes or myeloid cells. Similarly, the capacity of B and T cells to upregulate the expression of activation antigens in response to mitogenic or inflammatory stimuli was not hindered by Pb exposure. Analysis of the ability of ex vivo-cultured splenocytes to secrete cytokines demonstrated a marked reduction in IFN-{gamma} and IL-12p40 production associated with Pb exposure. In contrast, secretion of IL-4 by splenocytes of Pb-treated mice was 3- to 3.6-fold higher than in normal mice. The increased capacity to produce IL-4 correlated with a shift in the in vivo anti-Salmonellamore » antibody response from the protective IgG2a isotype to the Th2-induced IgG1 isotype. We conclude that chronic exposure to high levels of Pb results in a state of immunodeficiency which is not due to an overt cytotoxic or immunosuppressive mechanism, but rather is largely caused by a shift in immune responsiveness to Th2-type reactions.« less

Authors:
 [1];  [2];  [2];  [3];  [3];  [4];  [3];  [5]
  1. Department of Biochemistry, Faculty of Medicine and Health Sciences, UAE University, Al Ain (United Arab Emirates)
  2. Department of Medical Microbiology, Faculty of Medicine and Health Sciences, UAE University, P.O. Box 17666, Al Ain (United Arab Emirates)
  3. Department of Pharmacology, Faculty of Medicine and Health Sciences, UAE University, Al Ain (United Arab Emirates)
  4. Department of Physiology, Faculty of Medicine and Health Sciences, UAE University, Al Ain (United Arab Emirates)
  5. Department of Medical Microbiology, Faculty of Medicine and Health Sciences, UAE University, P.O. Box 17666, Al Ain (United Arab Emirates). E-mail: ramadi.b@uaeu.ac.ae
Publication Date:
OSTI Identifier:
20976855
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 218; Journal Issue: 3; Other Information: DOI: 10.1016/j.taap.2006.11.018; PII: S0041-008X(06)00434-0; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ACETATES; ANTIBODIES; ANTIGENS; CHICKENS; CHRONIC EXPOSURE; DRINKING WATER; IN VIVO; INFLAMMATION; LEAD; LYMPHOCYTES; LYMPHOKINES; MICE; MORTALITY; ORGANS; PATHOGENS; SALMONELLA; SECRETION

Citation Formats

Fernandez-Cabezudo, Maria J., Ali, Sumaya A.E., Ullah, Azim, Hasan, Mohammed Y., Kosanovic, Melita, Fahim, Mohamed A., Adem, Abdu, and Al-Ramadi, Basel K. Pronounced susceptibility to infection by Salmonella enterica serovar Typhimurium in mice chronically exposed to lead correlates with a shift to Th2-type immune responses. United States: N. p., 2007. Web. doi:10.1016/j.taap.2006.11.018.
Fernandez-Cabezudo, Maria J., Ali, Sumaya A.E., Ullah, Azim, Hasan, Mohammed Y., Kosanovic, Melita, Fahim, Mohamed A., Adem, Abdu, & Al-Ramadi, Basel K. Pronounced susceptibility to infection by Salmonella enterica serovar Typhimurium in mice chronically exposed to lead correlates with a shift to Th2-type immune responses. United States. doi:10.1016/j.taap.2006.11.018.
Fernandez-Cabezudo, Maria J., Ali, Sumaya A.E., Ullah, Azim, Hasan, Mohammed Y., Kosanovic, Melita, Fahim, Mohamed A., Adem, Abdu, and Al-Ramadi, Basel K. Thu . "Pronounced susceptibility to infection by Salmonella enterica serovar Typhimurium in mice chronically exposed to lead correlates with a shift to Th2-type immune responses". United States. doi:10.1016/j.taap.2006.11.018.
@article{osti_20976855,
title = {Pronounced susceptibility to infection by Salmonella enterica serovar Typhimurium in mice chronically exposed to lead correlates with a shift to Th2-type immune responses},
author = {Fernandez-Cabezudo, Maria J. and Ali, Sumaya A.E. and Ullah, Azim and Hasan, Mohammed Y. and Kosanovic, Melita and Fahim, Mohamed A. and Adem, Abdu and Al-Ramadi, Basel K.},
abstractNote = {Persistent exposure to inorganic lead (Pb) is known to adversely affect the immune system. In the present study, we assessed the effect of chronic Pb exposure on susceptibility to infection by the facultative intracellular pathogen Salmonella enterica serovar Typhimurium. Mice were exposed to 10 mM Pb-acetate in drinking water for {approx} 16 weeks, resulting in a significant level of Pb in the blood (106.2 {+-} 8.9 {mu}g/dl). Pb exposure rendered mice susceptible to Salmonella infection, manifested by increased bacterial burden in target organs and heightened mortality. Flow cytometric analysis of the splenic cellular composition in normal and Pb-exposed mice revealed no gross alteration in the ratios of B and T lymphocytes or myeloid cells. Similarly, the capacity of B and T cells to upregulate the expression of activation antigens in response to mitogenic or inflammatory stimuli was not hindered by Pb exposure. Analysis of the ability of ex vivo-cultured splenocytes to secrete cytokines demonstrated a marked reduction in IFN-{gamma} and IL-12p40 production associated with Pb exposure. In contrast, secretion of IL-4 by splenocytes of Pb-treated mice was 3- to 3.6-fold higher than in normal mice. The increased capacity to produce IL-4 correlated with a shift in the in vivo anti-Salmonella antibody response from the protective IgG2a isotype to the Th2-induced IgG1 isotype. We conclude that chronic exposure to high levels of Pb results in a state of immunodeficiency which is not due to an overt cytotoxic or immunosuppressive mechanism, but rather is largely caused by a shift in immune responsiveness to Th2-type reactions.},
doi = {10.1016/j.taap.2006.11.018},
journal = {Toxicology and Applied Pharmacology},
number = 3,
volume = 218,
place = {United States},
year = {Thu Feb 01 00:00:00 EST 2007},
month = {Thu Feb 01 00:00:00 EST 2007}
}
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