CCR2 mediates homeostatic and inflammatory release of Gr1(high) monocytes from the bone marrow, but is dispensable for bladder infiltration in bacterial urinary tract infection.
CCR2 is thought to recruit monocytes to sites of infection. Two subpopulations of murine blood monocytes differing in Gr1 and CCR2 expression have been described. The exact role of CCR2 in migration of CCR2(low)Gr1(low) and CCR2(high)Gr1(high) monocytes into nonlymphoid tissue is controversial. In this study, we have addressed this question in a murine model of bacterial urinary tract infection. Only Gr1(high) monocytes were recruited into the infected bladder. CCR2 deficiency reduced their frequency in this organ, indicating a requirement of this chemokine receptor. Importantly, CCR2-deficient mice also showed reduced Gr1(high) monocyte numbers in the blood, but not in the bone marrow (BM), indicating that CCR2 acted at the step of monocyte release into the circulation. The same was found also in noninfected mice, indicating a further involvement of CCR2 in steady-state BM egress. An additional requirement of CCR2 in monocyte recruitment from the blood into the bladder was excluded by tracking particle-labeled endogenous monocytes and by adoptive transfer of BM-derived monocyte subsets. These findings demonstrate that CCR2 governs homeostatic and infection-triggered release of Gr1(high) monocytes from the BM into the blood but is dispensable for recruitment into a nonlymphoid tissue.
Engel
Daniel R
DR
Institute for Molecular Medicine and Experimental Immunology, Rheinische Friedrich-Wilhelms-Universität, Bonn, Germany. daniel.engel@uni-bonn.de
Maurer
Juliane
J
Tittel
André P
AP
Weisheit
Christina
C
Cavlar
Taner
T
Schumak
Beatrix
B
Limmer
Andreas
A
van Rooijen
Nico
N
Trautwein
Christian
C
Tacke
Frank
F
Kurts
Christian
C
D000818:Animals; D000950:Antigens, Ly / Q000235:genetics / Q000276:immunology*; D001424:Bacterial Infections / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology*; D006706:Homeostasis / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009000:Monocytes / Q000276:immunology*; D054390:Receptors, CCR2 / Q000235:genetics / Q000276:immunology*; D001743:Urinary Bladder / Q000276:immunology* / Q000382:microbiology; D014552:Urinary Tract Infections / Q000235:genetics / Q000276:immunology*
D000950:Antigens, Ly; C515335:Ccr2 protein, mouse; C526827:Ly6 protein, mouse; D054390:Receptors, CCR2