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Evolutionary genetics: Ambiguous role of CCR5 in Y. pestis infection

Stephen J Elvin1, E Diane Williamson, Joanne C Scott

  • 1Defence Science and Technology Laboratories, Porton Down, Salisbury SP4 0JQ, UK.

Nature
|July 27, 2004
PubMed

Insights

Chemokine receptor CCR5 deficiency does not protect mice against plague. However, Ccr5-deficient macrophages showed reduced uptake of Yersinia pestis bacteria in vitro, suggesting a complex role for CCR5 in plague infection.

Area of Science:

  • Immunology
  • Microbiology
  • Genetics

Background:

  • The CCR5 receptor plays a role in immune responses.
  • A common CCR5 gene mutation (CCR5Delta32) in Caucasians was hypothesized to offer protection against plague.
  • Previous studies suggested CCR5 deficiency may not protect against Yersinia pestis infection.

Purpose of the Study:

  • To investigate the role of chemokine receptor CCR5 in Yersinia pestis infection.
  • To test the hypothesis that CCR5Delta32 mutation confers protection against plague.
  • To analyze the impact of Ccr5 deficiency on Yersinia pestis uptake by macrophages.

Main Methods:

  • Infection of Ccr5-deficient and wild-type mice with Yersinia pestis.
  • In vitro phagocytosis assays using macrophages from Ccr5-deficient and wild-type mice.
  • Survival analysis of infected mice.

Main Results:

  • No significant difference in survival rates between Ccr5-deficient and wild-type mice infected with Yersinia pestis.
  • Significantly reduced uptake of Yersinia pestis by Ccr5-deficient macrophages in vitro.
  • The CCR5Delta32 mutation's protective role against plague remains uncertain.

Conclusions:

  • CCR5 deficiency does not appear to confer protection against plague in a mouse model.
  • Ccr5 plays a role in the uptake of Yersinia pestis by macrophages, indicating a more complex involvement in infection than previously understood.
  • Further research is needed to elucidate the precise role of CCR5 in host defense against plague.

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