Study Pinpoints Molecule with Frontline Role in Immune Defenses Against Pneumonia

Study Pinpoints Molecule with Frontline Role in Immune Defenses Against Pneumonia

Researchers have discovered that a molecule with an apparently essential role in the body’s natural ability to fight pneumonia, although not quite the role they thought it would have. The discovery, made in mice, raises new questions to explore, but may also shed light on new ways of boosting patients’ immune defenses against the bacterial infection.

The study, “M-CSF Mediates Host Defense during Bacterial Pneumonia by Promoting the Survival of Lung and Liver Mononuclear Phagocytes,” published in the Journal of Immunology, focused on the role and mechanism of action of the cytokine macrophage-colony stimulating factor (M-CSF).

Researchers at the University of Virginia School of Medicine, looking into ways of improving the body’s natural defenses, found that mice infected with bacterial pneumonia and lacking M-CSF had the worst outcomes in terms of survival, bacterial load, and lung injury. Specifically, the scientists observed that the loss of this molecule resulted in 10 times more bacteria in their lungs, and 1,000 times more in the blood that spread the infection to their livers.

Such results made it clear that M-CSF has an important role in combating pneumonia, leading the scientists to further investigate its mechanisms. “M-CSF has previously been shown to help make a type of immune cell, called monocytes, so my idea was that if you take it away, infected hosts just stop making monocytes and that’s why they get sick,” Dr. Borna Mehrad, the study’s lead author, said in a press release, “and it turned out that was completely wrong.”

In a discovery credited to PhD student Alexandra Bettina, the researchers found that the absence of the cytokine does not affect the number of monocytes in the bone marrow, where the cells are made, or in the blood, through which they travel to the lung. But their numbers were vastly reduced in the lungs, meaning that monocytes are still being produced (and the hypothesis was wrong) — but in the absence of M-CSF, they’re not surviving for very long in an infected lung.

It wasn’t M-CSF’s role in monocyte production that was the issue, but how M-CSF helped monocytes to survive once they reached infected tissues.

“To use an analogy, they [monocytes] are like soldiers mobilizing,” Mehrad said. “They’re being made in the right number, they’re arriving in the right number, but when they get there, they’re not very good soldiers.”

Researchers believe more study, some important therapy questions, remain. Among those questions: M-CSF is clearly needed to fight infections, but since its production continues in infected hosts, would adding more really help? Or, might more simply be better for people with weakened immunity, who “might not make enough of M-CSF?” Mehrad said. Or, he further wondered, might more M-CSF indeed be of use to all, because a “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.”

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