Evolutionary genetics: Ambiguous role of CCR5 in Y. pestis infection.
Mecsas and colleagues suggest that a deficiency in the chemokine receptor CCR5 in humans is unlikely to confer protection against plague, based on their study of Yersinia pestis infection in Ccr5-deficient mice. They were testing the hypothesis that a mutation in the CCR5 gene, frequently found in Caucasians, may have been selected for in the past because it provided protection against (bubonic) plague; the mutation, called CCR5Delta32, is characterized by a 32-base-pair deletion. We have also tested this hypothesis by using Y. pestis infection in mice and, in addition, we have done phagocytosis experiments with macrophages from wild-type and Ccr5-deficient mice. Although, like Mecsas et al., we did not see any difference in the survival of the two groups of mice, we did find that there was a significantly reduced uptake of Y. pestis by Ccr5-deficient macrophages in vitro. Our results indicate that the role of Ccr5 in Y. pestis infection may therefore be more complex than previously thought.
Defence Science and Technology Laboratories, Porton Down, Salisbury SP4 0JQ, UK.
Stephen J
SJ
Elvin
E Diane
ED
Williamson
Joanne C
JC
Scott
Jeremy N
JN
Smith
Guillermo
G
Pérez De Lema
Silvia
S
Chilla
Paul
P
Clapham
Klaus
K
Pfeffer
Detlef
D
Schlöndorff
Bruno
B
Luckow
D000818:Animals; D019143:Evolution, Molecular; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D010587:Phagocytosis; D010930:Plague / Q000235:genetics* / Q000378:metabolism* / Q000382:microbiology; D019713:Receptors, CCR5 / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D017384:Sequence Deletion / Q000235:genetics; D015996:Survival Rate; D014774:Virulence; D044465:White People / Q000235:genetics; D015010:Yersinia pestis / Q000472:pathogenicity / Q000502:physiology
D019713:Receptors, CCR5