Up-regulation of tumor necrosis factor-alpha and interferon-gamma expression in the spleen and lungs of mice infected with the human Babesia isolate WA1

We analyzed cytokine expression in mice infected with the intraerythrocytic parasites Babesia microti and WA1. In C3H/HeN mice, WA1 infections were fa tal, whereas B. microti infections were resolved. We propose that the proin flammatory cytokines tumor necrosis factor-alpha (TNF alpha) and interferon -gamma (IFN gamma) contribute to the WA1-associated disease. WA1 infection was characterized by up-regulation of TNF alpha and IFN gamma mRNA in the s pleen. Previous studies in WA1-infected mice showed that pathologic lesions occurred primarily in the lungs, including pulmonary edema and intravascul ar margination of leukocytes. Analysis of cytokine expression in the lungs is important for an understanding of the disease process in WA1-infected mi ce. Expression of both TNF alpha and IFN gamma mRNA was increased in the lu ngs of WA1-infected mice. Immunohistochemical staining confirmed the upregu lation of these proinflammatory cytokines in the lungs. Expression of TNF a lpha and IFN gamma was not up-regulated in the lungs of B. microti-infected mice. The results implicate TNF alpha and IFN gamma in the pathogenesis of WA1-associated disease.