Proliferation of Ly6C+ monocytes regulated by IL-6

This interesting publication highlighted in the January edition of the Journal of Leukocyte Biology focuses on mucosal immune responses in urinary tract infection. Specifically, the team around Dixit and Engel showed that monocytes proliferate locally in the lamina propria of the bladder during experimental urinary tract infection in an IL-6 dependent manner. Importantly, this publication adds to other recent papers that challenge our concept of peripheral monocytes and macrophages as terminally differentiated cells.

Monocytes are key components of the innate immune defense against infections. These cells can be classified as inflammatory Ly6C+CCR2+CX3CR1int cells and patrolling Ly6C−CCR2−CX3CR1hi cells. Ly6C+ monocytes play an important role in the immune defense against infection and are especially crucial to fight urinary tract infections. Proliferation of Ly6C+ monocytes and their progenitors in the bone marrow has been shown in mice with systemic infection due to Listeria monocytogenes. Moreover, monocyte proliferation has shown to be regulated by the growth factor M-CSF. However, the proliferative capacity of Ly6C+ monocytes during infections remains unclear.

The cytokine IL-6 has been shown to be critical in inflammatory diseases in which monocyte accumulation occurs. In urinary tract infection, IL-6 is highly expressed and reduced IL-6 levels causes enhanced susceptibility to infection. Moreover, epithelial cells have been shown to be the major source of IL-6 in the infected bladder. Previously, two distinct modes of IL-6 signaling have been described…

Read more in: Dixit A, Bottek J, Beerlage A-L, et al. Frontline Science: Proliferation of Ly6C+ monocytes during urinary tract infections is regulated by IL-6 trans-signaling. J Leukoc Biol. 2018;103:13–22.