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Immunological Mechanisms Underlying the Genetic Predisposition to Severe Staphylococcus aureus Infection in the Mouse Model

von Kockritz-Blickwede, Maren; Rohde, Manfred; Oehmcke, Sonja LU ; Miller, Lloyd S.; Cheung, Ambrose L.; Herwald, Heiko LU ; Foster, Simon and Medina, Eva (2008) In American Journal of Pathology 173(6). p.1657-1668
Abstract
Host genetic variations play a significant role in conferring predisposition to infection. in this study, we examined the immune mechanisms underlying the host genetic predisposition to severe Staphylococcus aureus infection in different mouse strains. Whereas C57BL/6 mice were the most resistant in terms of control of bacterial growth and survival, A/J, DBA/2, and BALB/c mice were highly susceptible and succumbed to infection shortly after bacterial inoculation. Other strains (C3H/HeN, CBA, and C57BL/10) exhibited intermediate susceptibility levels. Susceptibility of mice to S. aureus was associated with an inability to limit bacterial growth in the kidneys and development of pathology. Resistance to S. aureus in C57BL/6 mice was... (More)
Host genetic variations play a significant role in conferring predisposition to infection. in this study, we examined the immune mechanisms underlying the host genetic predisposition to severe Staphylococcus aureus infection in different mouse strains. Whereas C57BL/6 mice were the most resistant in terms of control of bacterial growth and survival, A/J, DBA/2, and BALB/c mice were highly susceptible and succumbed to infection shortly after bacterial inoculation. Other strains (C3H/HeN, CBA, and C57BL/10) exhibited intermediate susceptibility levels. Susceptibility of mice to S. aureus was associated with an inability to limit bacterial growth in the kidneys and development of pathology. Resistance to S. aureus in C57BL/6 mice was dependent on innate immune mechanisms because Rag2-IL2R gamma(-/-) C57BL/6 mice, which are deficient in B, T, and NK cells, were also resistant to infection. Indeed, neutrophil depletion or inhibition of neutrophil recruitment rendered C57BL/6 mice completely susceptible to S. aureus, indicating that neutrophils are essential for the observed resistance. Although neutrophil function is not inhibited in A/J mice, expression of neutrophil chemoattractants; KC and MIP-2 peaked earlier in the kidneys of C57BL/6 mice than in A/J mice, indicating that a delay in neutrophil recruitment to the site of infection may underlie the increased susceptibility of A/J mice to S. aureus. (Am J Pathol 2008,173:1657-1668, DOI: 10.2353/ajpath.2008.080337) (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
American Journal of Pathology
volume
173
issue
6
pages
1657 - 1668
publisher
American Society for Investigative Pathology
external identifiers
  • wos:000261253500008
  • scopus:57149109128
ISSN
1525-2191
DOI
10.2353/ajpath.2008.080337
language
English
LU publication?
yes
id
238da97d-0247-4bdd-b1bb-7b757d6a9ff8 (old id 1308016)
date added to LUP
2009-03-19 14:34:50
date last changed
2017-06-25 03:40:22
@article{238da97d-0247-4bdd-b1bb-7b757d6a9ff8,
  abstract     = {Host genetic variations play a significant role in conferring predisposition to infection. in this study, we examined the immune mechanisms underlying the host genetic predisposition to severe Staphylococcus aureus infection in different mouse strains. Whereas C57BL/6 mice were the most resistant in terms of control of bacterial growth and survival, A/J, DBA/2, and BALB/c mice were highly susceptible and succumbed to infection shortly after bacterial inoculation. Other strains (C3H/HeN, CBA, and C57BL/10) exhibited intermediate susceptibility levels. Susceptibility of mice to S. aureus was associated with an inability to limit bacterial growth in the kidneys and development of pathology. Resistance to S. aureus in C57BL/6 mice was dependent on innate immune mechanisms because Rag2-IL2R gamma(-/-) C57BL/6 mice, which are deficient in B, T, and NK cells, were also resistant to infection. Indeed, neutrophil depletion or inhibition of neutrophil recruitment rendered C57BL/6 mice completely susceptible to S. aureus, indicating that neutrophils are essential for the observed resistance. Although neutrophil function is not inhibited in A/J mice, expression of neutrophil chemoattractants; KC and MIP-2 peaked earlier in the kidneys of C57BL/6 mice than in A/J mice, indicating that a delay in neutrophil recruitment to the site of infection may underlie the increased susceptibility of A/J mice to S. aureus. (Am J Pathol 2008,173:1657-1668, DOI: 10.2353/ajpath.2008.080337)},
  author       = {von Kockritz-Blickwede, Maren and Rohde, Manfred and Oehmcke, Sonja and Miller, Lloyd S. and Cheung, Ambrose L. and Herwald, Heiko and Foster, Simon and Medina, Eva},
  issn         = {1525-2191},
  language     = {eng},
  number       = {6},
  pages        = {1657--1668},
  publisher    = {American Society for Investigative Pathology},
  series       = {American Journal of Pathology},
  title        = {Immunological Mechanisms Underlying the Genetic Predisposition to Severe Staphylococcus aureus Infection in the Mouse Model},
  url          = {http://dx.doi.org/10.2353/ajpath.2008.080337},
  volume       = {173},
  year         = {2008},
}