6533b7d5fe1ef96bd126534f

RESEARCH PRODUCT

TLR3-independent activation of mast cells by cytomegalovirus contributes to control of pulmonary infection.

subject

description

Interstitial pneumonia is a life-threatening clinical manifestation of human cytomegalovirus (hCMV) infection. In particular, it can be deadly in patients with hematopoietic malignancies who undergo hematopoietic cell transplantation (HCT) in whom a ‘window of risk’, which is defined by transient immunodeficiency, occurs between hematoablative therapeutic treatment and immunological reconstitution. As few clinical studies have addressed the underlying mechanisms for this phenomenon, a mouse model of HCT and murine cytomegalovirus (mCMV) infection has been established and has revealed a key role for antiviral CD8+ T cells in controlling pulmonary infections. Using this mouse model, recent studies have provided evidence for the role of mast cells (MC) in more efficiently recruiting antiviral CD8+ T cells to CMV-infected lungs in a process that involves the release of CCL5, a chemokine. MC were found to be direct cellular targets of murine CMV infection and could be activated and degranulated by two mechanisms: the rapid degranulation requiring TLR3/TRIF signaling in non-MC cells and a delayed TLR3/TRIF-independent mechanism. Here, we provide evidence showing that TLR3/TRIF-independent MC activation by CMV is the dominant mechanism in controlling pulmonary infection.