Submitted to: Infection and Immunity
Publication Type: Peer reviewed journal
Publication Acceptance Date: 3/12/2004
Publication Date: 7/15/2004
Citation: Liu, Q., Callendar, C., Liu, Q., Whitmire, J., Grusby, M., Finkleman, F., Darling, T., Cheever, A., Swearengen, J., Urban Jr, J.F. 2004. Simultaneous deficiency in cd28 and stat6 results in chronic ectoparasites-induced inflammatory skin disease. Infection and Immunity. 72:3706-3715 (2004) Interpretive Summary: Immunity to surface dwelling skin parasites such as skin mites is not well described, but there is a component of protective immunity that is characterized by an ability to develop strong immediate type hypersensitivity reaction that result in parasite exclusion. Many skin mites go undetected because they establish a commensal relationship that does not trigger a severe immune response except under conditions where the immune system is compromised. This is the case during HIV infection or other infections that induce an immune deficiency or when individuals are treated with immune suppressive drugs for therapy of autoimmune diseases and cancer. The expression of more severe mite infection can be a result of immune suppression. This report shows that undetected mite infection in mice can become exacerbated when specific cell markers are absent from the mouse. The markers are easily detected and can be used as indicate if a mite infection will become a problem under conditions where the immune system is compromised. This work will have importance to animal managers of research animal facilities because it provides an explanation for severe mite infection in normal mice, and can be useful to both clinicians and those interested in treated parasitic diseases of the skin.
Technical Abstract: A mouse lacking CD28, a T cell co stimulatory molecule, and STAT6, a transcription factor that mediates IL-4 signaling, was developed from parental CD28 and STAT6 deficient mice. STAT6/CD28-/- BALB/c mice at 8 weeks showed a normal phenotype and IL-4 production was induced following infection with nematode parasites. Unexpectedly, between four to eight months of age, all mice examined spontaneously developed severe chronic dermatitis associated with pronounced numbers of Demodex ectoparasites. In addition, pronounced CD4 and CD8 T cell infiltrates in the dermis and subcutaneous fat, increased serum IgG2a, and lymphadenopathy, associated with increased IFN-gamma and IL-12 expression, were observed. Single knockout siblings lacking either CD28 or STAT6 maintained a phenotype similar to BALB/c wildtype controls. To distinguish whether the ectoparasite, Demodex, or the Th1 immunity, were the proximal cause of the inflammatory skin disease STAT6/CD28-/- mice were treated with a miticide that eliminated the ectoparasites. This treatment also markedly reduced the severity of the dermatitis and the associated lymphoid infiltrates. These findings suggest that ubiquitous ectoparasites, generally considered commensal, may contribute to disease when specific molecules required for an effective Th2 response are blocked