Systemic responses during local viral infections: type I IFNs sound the alarm

Abstract

Type I IFNs are well known for their role in controlling virus replication and spread. Type I IFNs produced by the infected tissue also signal beyond the boundaries of the infection to regulate different elements of the anti-viral immune response. Recent reports show that type I IFNs directly condition naive monocytes residing in the distal bone marrow (BM) and induce the expression of effector molecules in memory T cells, before their recruitment to the infected site. In addition, hematopoietic stem cells (HSCs) were shown to enter the cell cycle in response to systemically distributed type I IFNs. These discoveries expand our understanding of the pleiotropic effects of type I IFNs during infection and highlight the critical role of systemic signals in the development of an effective response to a localized viral infection.

Figure 1. Systemic responses to localized virus infections

Pro-inflammatory signals produced in the infected tissue are disseminated systemically during a localized virus infection. Some of the effects of these systemic signals, such as the induction of fever, have been appreciated for a long time, but a number of others have only recently been recognized. These include the stimulation of the hypothalamic-pituitary-adrenal axis due to physiological stress at the infected site [42], the anti-viral conditioning of leukocytes residing in the bone marrow at the time of infection [9], and the antigen-independent activation of memory T cells during the course of respiratory viral infections [33].