Myeloid cell responsiveness to interferon-gamma is sufficient for initial resistance to Listeria monocytogenes

• Published in: Current research in immunology 2020-12, Vol.1, p.1-9
• Main Authors: Eshleman, Emily M., Bortell, Nikki, McDermott, Daniel S., Crisler, William J., Lenz, Laurel L.
• Format: Article
• Language: English
• Subjects: IFNGR; IFNγ; Infection; Listeria monocytogenes; Myeloid cells
• ISSN: 2590-2555; 2590-2555
• DOI: 10.1016/j.crimmu.2020.01.001

The type II interferon (IFNγ) promotes resistance to intracellular pathogens. Most immune and somatic cells also express the IFNγ receptor (IFNGR) and respond to IFNγ. While myeloid cell have been implicated as important targets of IFNγ, it remains unknown if IFNγ signaling to myeloid cell types suffices for resistance to infection. Here, we addressed this question by generating mice in which IFNGR1 is selectively expressed by myeloid cells. These “MSGR1” (myeloid selective IFNGR1) mice express an epitope-tagged Ifngr1 transgene (fGR1) from the myeloid-specific c-fms promoter in a background lacking endogenous Ifngr1. IFNGR staining was selectively observed on myeloid cells in the MSGR1 mice and correlated with responsiveness of these cells to IFNγ. During systemic infection by the bacterium Listeria monocytogenes, activation marker staining was comparable on monocytes from MSGR1 and control B6 mice. Bacterial burdens and survival were also equivalent in MSGR1 and wildtype B6 animals at a timepoint when B6.Ifngr1−/− mice began to succumb. These data confirm that activation of inflammatory monocytes and neutrophils is a key mechanism by which IFNγ promotes innate anti-bacterial immunity and suggest that IFNγ targeting of myeloid cells is largely sufficient to mediate protection against systemic L. monocytogenes. [Display omitted] •Expression of IFNGR1 is restricted to monocytes and neutrophils in “MSGR1” (myeloid selective IFNGR1) mice.•Myeloid cells from MSGR1 mice are responsive to IFNγ and show elevated activation compared to cells from B6.Ifngr1−/− mice.•MSGR1 myeloid cells respond to Listeria monocytogenes infection and promote early resistance.•IFNγ stimulation of myeloid cells can thus protect against infection independent of effects on other hematopoietic and non-hematopoietic cell populations.•Particularly in female mice, IFNγ stimulation of non-myeloid cells may also contribute to improved survival.