Absence of CC chemokine ligand 2 results in an altered Th1/Th2 cytokine balance and failure to expel Trichuris muris infection.
Despite a growing understanding of the role of cytokines in immunity to intestinal helminth infections, the importance of chemokines has been neglected. As a chemokine with both chemoattractive properties and an ability to shape the quality of the adaptive immune response, CC chemokine ligand 2 (CCL2) was investigated as an attractive candidate for controlling resistance to these types of infection, which require highly polarized Th cell responses. We show here for the first time that CCL2 plays an important role in the development of resistance to infection by the gastrointestinal nematode Trichuris muris. Thus, in the absence of CCL2, worm expulsion does not occur, and the lymph node draining the site of infection becomes a Th1-promoting environment. Elevated levels of IL-12 are produced by polarizing APCs, and the composition of the APC environment itself is perturbed, with reduced numbers of macrophages.
deSchoolmeester
Matthew L
ML
Department of Immunology, Microbiology, and Development, University of Manchester School of Biological Sciences, Manchester, United Kingdom. matthew.deschoolmeester@man.ac.uk
Little
Matthew C
MC
Rollins
Barrett J
BJ
Else
Kathryn J
KJ
D000818:Animals; D018932:Chemokine CCL2 / Q000378:metabolism*; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D020022:Genetic Predisposition to Disease; D007113:Immunity, Innate / Q000235:genetics; D007411:Intestinal Diseases, Parasitic / Q000235:genetics / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D007420:Intestine, Large / Q000276:immunology / Q000473:pathology; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000473:pathology; D008297:Male; D008643:Mesentery; D051379:Mice; D008806:Mice, Inbred AKR / Q000097:blood; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D013045:Species Specificity; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D014257:Trichuriasis / Q000235:genetics / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D014258:Trichuris / Q000254:growth & development / Q000276:immunology*
C515335:Ccr2 protein, mouse; D018932:Chemokine CCL2; D016207:Cytokines; D054390:Receptors, CCR2; D019707:Receptors, Chemokine