Adhesion molecules and
cytokines are involved in regulation of cellular host responses in
infection processes. In this study the roles of the
integrins Mac-1 and
VLA-4, as well as those of the
cytokines tumor necrosis factor alpha (
TNF-alpha) and
gamma interferon (IFN-gamma), in defense mechanisms against Yersinia enterocolitica in Peyer's patches (PP) and mesenteric lymph nodes (MLN) were investigated by blocking these molecules with
antibodies in vivo prior to orogastric
Yersinia infection. Intestinal
Yersinia infection caused
abscesses composed of polymorphonuclear (Mac-1+ VLA-4+ Pgp-1+ ICAM-1-) and mononuclear (Mac-1+ VLA-4+ Pgp-1+ ICAM-inhibited phagocytosis of yersiniae by macrophages, (ii) reduced Yersinia-specific proliferation and IFN-gamma production of T cells from PP and MLN, and (iii) caused increased bacterial growth in PP and MLN followed by profound tissue destruction. Neutralization of
TNF-alpha or IFN-gamma had comparable effects, suggesting that cell-mediated host responses including activated macrophages are required for control of yersiniae in intestinal tissues. The number of Mac-1+ cells in PP and MLN increased after
yersinia infection, and recruitment of these cells was not blocked by administration of anticytokine or anti-
integrin antibodies. While anti-VLA-4, -
TNF-alpha, or -IFN-gamma antibody treatment caused an increased dissemination of yersiniae from PP to the spleen systemic dissemination was reduced by anti-Mac-1
antibodies. The results of this study suggest that the
cytokines IFN-gamma and
TNF-alpha as well as the
integrins Mac-1 and VLA-4 are involved in protective cellular host defense mechanisms in PP and MLN against Y. enterocolitica, the latter probably being involved in both cell-cell and cell-pathogen interactions.