Ib. Autenrieth et al., DEFENSE-MECHANISMS IN PEYERS-PATCHES AND MESENTERIC LYMPH-NODES AGAINST YERSINIA-ENTEROCOLITICA INVOLVE INTEGRINS AND CYTOKINES, Infection and immunity, 64(4), 1996, pp. 1357-1368
Adhesion molecules and cytokines are involved in regulation of cellula
r host responses in infection processes. In this study the roles of th
e integrins Mac-1 and VLA-4, as well as those of the cytokines tumor n
ecrosis 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 th
ese molecules with antibodies in vivo prior to orogastric Yersinia inf
ection. Intestinal Yersinia infection caused abscesses composed of pol
ymorphonuclear (Mac-1(+) VLA-4(-) Pgp-1(+) ICAM-1(-)) and mononuclear
(Mac-1(+) VLA-4(+) Pgp-1(+) ICAM-1(+)) phagocytes and formation of MAd
CAM-1(+) venules in PP and MLN. Blocking of Mac-1 or VLA-4 (i) inhibit
ed phagocytosis of yersiniae by macrophages, (ii) reduced Yersinia-spe
cific proliferation and IFN-gamma production of T cells from PP and ML
N, and (iii) caused increased bacterial growth in PP and MLN followed
by profound tissue destruction. Neutralization of TNF-alpha or IFN-gam
ma had comparable effects, suggesting that fell-mediated host response
s including activated macrophages are required for control of yersinia
e in intestinal tissues. The number of Mac-1(+) cells in PP and MLN in
creased after yersinia infection, and recruitment of these cells was n
ot blocked by administration of anticytokine or anti-integrin antibodi
es. While anti-VLA-4, -TNF-alpha, or -IFN-gamma antibody treatment cau
sed an increased dissemination of yersiniae from PP to the spleen, sys
temic dissemination was reduced by anti-Mac-1 antibodies. The results
of this study suggest that the cytokines IFN-gamma and TNF-alpha as we
ll as the integrins Mac-1 and VLA-4 are involved in protective cellula
r host defense mechanisms in PP and MLN against Y. enterocolitica, the
latter probably being involved in both cell-cell and cell-pathogen in
teractions.