title: Age-dependent role for CCR5 in antiviral host defense against herpes simplex virus type 2.
abstract: Elimination of viral infections is dependent on rapid recruitment and activation of leukocytes with antiviral activities to infected areas. Chemokines constitute a class of cytokines that have regulatory effects on leukocyte migration and activity. In this study we have studied the role of CC chemokine receptor 1 (CCR1) and CCR5 in host defense during a generalized herpes simplex virus type 2 (HSV-2) infection. Whereas both 4- and 8-week-old CCR1(-/-) mice resembled wild-type mice (C57BL/6) with respect to defense against the infection, significantly higher virus titers were seen in the livers and brains of 4-week-old CCR5(-/-) mice. At the age of 8 weeks, CCR5(-/-) were indistinguishable from wild-type mice and cleared the infection from liver and spleen. Although 4-week-old CCR5(-/-) mice were able to recruit natural killer (NK) cells to the site of infection, these cells had reduced cytotoxic activity compared to NK cells from wild-type mice. This was not due to lower production of alpha/beta interferon or interleukin-12, two well-described activators of cytotoxic activity in NK cells. We also noted that the spleens of young CCR5(-/-) mice did not increase in size during infection as did the spleens of wild-type and CCR1(-/-) mice. This observation was accompanied by impaired proliferation of CCR5(-/-) splenocytes (SCs) ex vivo. Moreover, migration of CD8(+) T cells to the liver in response to infection was impaired in CCR5(-/-) mice, and adoptive transfer of SCs from CCR5(-/-) mice infected for 6 days into newly infected wild-type mice did not improve antiviral activity in the liver, in contrast to what was seen in mice receiving immune SCs from wild-type mice. Altogether, this study shows that CCR5 plays an age-dependent role in host defense against HSV-2 by supporting both the innate and adaptive immune response.
authors: Institute of Medical Microbiology and Immunology, University of Aarhus, Denmark.
authors: Nina
authors: N
authors: Ank
authors: Klavs
authors: K
authors: Petersen
authors: Lene
authors: L
authors: Malmgaard
authors: Søren C
authors: SC
authors: Mogensen
authors: Søren R
authors: SR
authors: Paludan
mesh_terms: D000367:Age Factors; D000818:Animals; D006561:Herpes Simplex / Q000276:immunology*; D018258:Herpesvirus 2, Human; D007110:Immunity, Active; D007113:Immunity, Innate; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019713:Receptors, CCR5 / Q000172:deficiency / Q000276:immunology*
chemical_list: D019713:Receptors, CCR5