Role of CD4 T cell mannose binding lectin in Schistosoma-induced pulmonary hypertension

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Abstract

Schistosomiasis is a common cause of pulmonary hypertension (PH) worldwide. It is known that adaptive immunity and specifically CD4 T cells are necessary for experimental disease pathogenesis. The lectin complement system is activated in those infected with schistosomiasis. We tested the hypothesis that lectin complement promotes Th2 CD4 T cell activation, leading to PH in a schistosomiasis exposure model. Wildtype and transgenic mice lacking mannose binding lectin (MBL), and bone marrow chimeras, were experimentally exposed to Schistosoma mansoni eggs. PH severity was assessed by hemodynamics and vascular remodeling, and CD4 T cell density and phenotype was assessed by flow cytometry. Wildtype recipients of MBL knockout bone marrow (BM) were protected from Schistosoma-induced PH. The protection from PH was associated with fewer Th2 CD4 T cells. In wildtype mice exposed to Schistosoma, CD4 T cells expression of MBL increased. MBL-deficient CD4 T cells had a suppressed Th2 phenotype when exposed to Schistosoma antigens. Mice with deficiency of C4, which functions downstream of MBL in the lectin complement pathway, were not protected from Schistosoma-PH. Mice lacking MBL were not protected from PH caused by hypoxia exposure. MBL in CD4 T cells promotes Schistosoma-induced PH.

Authors

Claudia Mickael, Dara C. Fonseca Balladares, Rahul Kumar, Michael H. Lee, Kevin Nolan, Linda Sanders, Katie J. Tuscan, Ramraj Prasad, Pilar Londono, Fernanda P. Oliveira, Kennedi B. Pyper, Ari B. Molofsky, Rubin M. Tuder, Kurt R. Stenmark, Brian B. Graham