Increased susceptibility of male BALB/c mice to coxsackievirus B3-induced myocarditis: role for CD1d.
BALB/c male mice infected with the H3 variant of coxsackievirus B3 (CVB3) develop fulminant myocarditis. Age-matched female mice show little myocarditis due to decreased virus receptor expression on cardiac cells. TNFalpha and IL-1beta levels were increased in males by 3 days after infection. IFNgamma levels increased more slowly throughout the 7-day observation period. CD4+, CD8+, macrophage (Mac3+) and gammadelta+ cells all accumulated in male hearts, with gammadelta+ cells showing early (day 3) infiltration. Females also accumulated CD4+ cells, but few of the other cell types. CD4+ cells in male hearts predominately produced IFNgamma, indicating a Th1 cell phenotype, whereas CD4+ cells in females produced IL-4, but little IFNgamma, indicating a Th2 phenotype. CD1d, a major histocompatibility complex I-like molecule often implicated in innate immunity, was increased in CVB3-infected male but not female cardiocytes both in vivo and in vitro. These results demonstrate that CVB3 infections produce gender-specific differences in both innate and adaptive immunity, which may explain the difference in disease susceptibility.
Huber
Sally A
SA
University of Vermont, Department of Pathology, 208 South Park Drive Suite 2, Colchester, VT 05446, USA. Sally.Huber@uvm.edu
D000818:Animals; D018949:Antigens, CD1 / Q000032:analysis / Q000502:physiology*; D055610:Antigens, CD1d; D015496:CD4-Positive T-Lymphocytes; D018414:CD8-Positive T-Lymphocytes; D003384:Coxsackievirus Infections / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D029822:Enterovirus B, Human; D005260:Female; D007371:Interferon-gamma / Q000032:analysis; D007375:Interleukin-1 / Q000032:analysis; D008264:Macrophages; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009205:Myocarditis / Q000276:immunology* / Q000821:virology; D009206:Myocardium / Q000276:immunology / Q000473:pathology; D032383:Myocytes, Cardiac / Q000276:immunology; D012727:Sex Characteristics; D018417:Th1 Cells; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D018949:Antigens, CD1; D055610:Antigens, CD1d; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma