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

Abstract

The migration of leukocytes to inflammatory sites elicited by Paracoccidioides brasiliensis is supposed to be coordinated by cytokines and chemokines. Here, we investigated the role of intercellular adhesion molecule-1 (ICAM-1) in recruiting inflammatory cells to lungs of mice infected with P. brasiliensis and in determining the outcome of the disease. Expression of ICAM-1 was up-regulated on T lymphocytes after infection with the fungus, and its expression was dependent on interferon-␥, tumor necrosis factor-␣, and interleukin-12. Moreover, the absence of ICAM-1 resulted in high susceptibility to the infection and delayed formation of granulomatous lesions. In addition, the absence of ICAM-1 resulted in increased growth and dissemination of fungus , decreased number of CD3 ؉ CD4 ؉ and CD3 ؉ CD8 ؉ T cells , and increased production of interleukin-4 in the inflammatory site. The organization of a granulomatous reaction in mice deficient of ICAM-1 was delayed , starting only on day 60 after infection , whereas in wild-type mice it was complete on day 30 of infection. These data show that ICAM-1 is effectively involved in cellular migration and in the organization of the granulomatous lesion caused by the fungus P.

Pulmonary immune responses induced in BALB/c mice by Paracoccidioides brasiliensis conidia

“…These data show that ICAM-1 is effectively involved in cellular migration and in the organization of the granulomatous lesion caused by the fungus P. brasiliensis [137]. Moreover, the absence of ICAM-1 resulted in high susceptibility to the infection, in increased growth and dissemination of fungus, decreased number of CD3+CD4+ and CD3+CD8+ T cells and increased production of interleukin-4 at the inflammatory site.…”

Interactions of Paracoccidioides brasiliensis with host cells: recent advances

“…More recently, recombinant 3-glyceraldeyde phosphate dehydrogenase (GAPDH) from P. brasiliensis was found to be capable of binding to laminin, collagen I, and fibronectin. P. brasiliensis yeast forms treated with anti-GAPDH were inhibited from infecting epithelial cells, and pneumocytes treated with recombinant GAPDH were resistant to fungal infection [36]. Paracoccin, a recently described adhesin, interacted with laminin in a dose-dependent manner.…”

“…In P. brasiliensis, some adhesins have been described, and it is believed that all can play important roles in pathogenesis [20,36,[39][40][41]. However, until now we have no P. brasiliensis strains with modified genes for these adhesins.…”

“…During this interaction, the fungal cell wall is in continual contact with the host and acts as a sieve and reservoir of molecules such as adhesins [20,35]. Our knowledge of the P. brasiliensis cell-surface structures and the basic mechanisms underlying their interaction with host receptor molecules has increased dramatically, through molecular and structural analysis of adherence molecules [20,36].…”

5-Lipoxygenase Activity Increases Susceptibility to Experimental Paracoccidioides brasiliensis Infection

“…The migration and activation of inflammatory cells in the granulomas during PCM has been associated with a more efficient control of fungal growth and dissemination (20). Therefore, we next evaluated the role of 5-LO-products in cellular recruitment.…”