Cytokine Required by Immune Cells in Lungs to Defend Against Pneumonia Infection

The cytokine macrophage-colony stimulating factor (M-CSF) was been found to play a critical role in the ability of immune cells in the lung to defend against infection by pneumonia-causing bacteria.

M-CSF is a hematopoietic growth factor that is involved in the proliferation, differentiation, and survival of monocytes, macrophages, and bone marrow progenitor cells. M-CSF affects macrophages and monocytes in several ways, including stimulating increased phagocytic and chemotactic activity, and increased tumor cell cytotoxicity.

To develop a better understanding of how M-CSF functions in the lungs, investigators at the University of Virginia (Charlottesville, USA) tested the hypothesis that M-CSF was required for mononuclear phagocyte-mediated host defenses during bacterial pneumonia in a mouse model of pneumonia infection.

They reported in the June 15, 2016, issue of The Journal of Immunology that in the mouse model system genetic deletion or immuno-neutralization of M-CSF resulted in reduced survival, increased bacterial burden, and greater lung injury. M-CSF was necessary for the expansion of lung mononuclear phagocytes during infection but did not affect the number of bone marrow or blood monocytes, proliferation of precursors, or recruitment of leukocytes to the lungs. In contrast, M-CSF was essential to the animals' survival and to antimicrobial functions of both lung and liver mononuclear phagocytes during pneumonia. The absence of M-CSF resulted in bacterial dissemination to the liver and hepatic necrosis.

"If you take M-CSF away, the infections get worse, so that raises two important questions about therapy: Would more be better? It may be that during infection, the body is making the right amount of M-CSF and if we add extra, it will not improve outcomes further," said senior author Dr. Borna Mehrad, associate professor of internal medicine and microbiology at the University of Virginia. "The second possibility is that there is room for improvement: in the fight between monocytes and the bacteria, M-CSF may make monocytes live longer and give them an edge. In addition, some people with weakened immunity might not make enough of M-CSF. If that is the case, you could augment that and improve their ability to fight the infection."

"We are interested in seeing if there are things we can do to strengthen the natural defenses of the host to help them fight the infection more effectively," said Dr. Mehrad. "Potentially this would be the sort of thing you could do in addition to antibiotics to help patients with severe infections."

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