Intercellular Adhesion Molecule 1 Deficiency Leads to Impaired Recruitment of T Lymphocytes and Enhanced Host Susceptibility to Infection withTrypanosoma cruzi

Abstract

In this study, we investigated the involvement of Th1 cytokines in the expression of cell adhesion molecules (CAM) and recruitment of inflammatory cells to the heart of mice infected with Trypanosoma cruzi. Our results show that endogenously produced IFN-γ is essential to induce optimal expression of VCAM-1 and ICAM-1 on the cardiac vascular endothelium of infected mice. Furthermore, the influx of inflammatory cells into the cardiac tissue was impaired in Th1 cytokine-deficient infected mice, paralleling the intensity of VCAM-1 and ICAM-1 expression on the vascular endothelium. Consistent with the importance of ICAM-1 in host resistance, ICAM-1 knockout (KO) mice were highly susceptible to T. cruzi infection, as assessed by mortality rate, parasitemia, and heart tissue parasitism. The enhanced parasitism was associated with a decrease in the numbers of CD4+ and CD8+ T lymphocytes in the heart tissue of ICAM-1 KO mice. Additionally, ICAM-1 KO mice mounted an unimpaired IFN-γ response and IFN-γ-dependent production of reactive nitrogen intermediates and parasite- specific IgG2a. Supporting the participation of ICAM-1 in cell migration during T. cruzi infection, the entrance of adoptively transferred PBL from T. cruzi-infected wild-type C57BL/6 mice into the cardiac tissue of ICAM-1 KO mice was significantly abrogated. Therefore, we favor the hypothesis that ICAM-1 plays a crucial role in T lymphocyte recruitment to the cardiac tissue and host susceptibility during T. cruzi infection.

Lipoprotein p37 from Mycoplasma hyorhinis inhibiting mammalian cell adhesion

“…Suppressed expression of VCAM-1 and ICAM-1 is associated with reduced adhesion of monocytes and lymphocytes to human umbilical vein endothelial cell stimulated by cytokine [20]. ICAM-1 plays a crucial role in Trypanosoma cruzi recruitment to the cardiac tissue and host susceptibility during T. cruzi infection [21]. Integrin b1-mediated cell adhesion regulates a multitude of cellular responses, including proliferation, survival and cross-talk between different cellular signaling pathways.…”

TNF/TNFR1 signaling up-regulates CCR5 expression by CD8+ T lymphocytes and promotes heart tissue damage during Trypanosoma cruzi infection: beneficial effects of TNF-α blockade

“…Furthermore, the decreased recruitment of cells to cardiac tissue in TNFR1 -/-infected mice was associated with diminished ICAM-1 expression by heart endothelial cells. Thus, it seems that the TNF/TNFR1 signaling pathway plays a crucial role in inflammatory cell extravasation to cardiac tissue by controlling the expression of CCR5 and ICAM-1, molecules involved in the establishment of T. cruzi-elicited myocarditis , Michailowsky et al 2004.…”

Intercellular Adhesion Molecule-1 Is Required for the Early Formation of Granulomas and Participates in the Resistance of Mice to the Infection with the Fungus Paracoccidioides brasiliensis

“…Indeed, in the present work, ICAM-1KO mice were more susceptible to infection than the littermate WT controls. Higher mortality and decreased migration of T lymphocytes to target organs were also found in animals deficient in ICAM-1 when infected with Trypanosoma cruzi 34 or Chlamydia trachomatis. 35 The greater susceptibility to infection in the absence of ICAM-1 could be attributable to the production of low levels of IFN-␥ and/or antibodies.…”

“…Accordingly, minimal effects on the generation of specific T-cell responses and humoral immunity were observed in the absence of ICAM in mice infected with the protozoa T. cruzi. 34 However, in infection with P. brasiliensis, its absence results in a delay of the DTH response to the specific antigens and increased production of IL-4 on day 15 after infection. The IL-4 could be produced by alveolar macrophages 40 and histiocytes, which are present in the lungs at this time of infection.…”