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.
Elvin
Stephen J
SJ
Defence Science and Technology Laboratories, Porton Down, Salisbury SP4 0JQ, UK.
Williamson
E Diane
ED
Scott
Joanne C
JC
Smith
Jeremy N
JN
Pérez De Lema
Guillermo
G
Chilla
Silvia
S
Clapham
Paul
P
Pfeffer
Klaus
K
Schlöndorff
Detlef
D
Luckow
Bruno
B
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