New Discovery Could Help People Fight Pneumonia

Researchers at the University of Virginia School of Medicine have made a discovery that could assist in increasing patients’ ability to fight off pneumonia, according to materials posted by The University of Virginia Health System. A molecule that has been targeted in cancer can also play a critical role in strengthening the immune system, and thus, work to boost patients’ ability to fight off the infection. The aim to strengthen the body has become even more important as antibiotic resistance continues to rise and effective treatment options continue to diminish.

Borna Mehrad, MBBS, of UVA’s Division of Pulmonary and Critical Care Medicine, explains that they aim to make the body of the host stronger in addition to the assistance of antibiotics in an effort to help patients combat severe infections.

The study focused on the cytokine macrophage-colony stimulating factor (M-CSF), also known as colony stimulating factor 1 (CSF1). According to the study published by The Journal of Immunology, “The mononuclear phagocyte system [MPS] is a heterogeneous group of leukocytes composed of tissue-resident macrophages, dendritic cells, and monocyte-derived cells that are critical in defense against pneumonia, but mechanisms that regulate their maintenance and function during infection are poorly defined.” M-CSF has a number of effects on the mononuclear phagocytes, yet, its role in pneumonia remains unknown.

In the materials published by the university, Mehrad explains his team’s initial hypothesis. He says, “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, and it turned out that was completely wrong.”

Mehrad and his team used a murine model of infection comprised of infected mice and found that lack of cytokine M-CSF worsened the outcome of bacterial pneumonia. The study found that 10 times more bacteria were found in the lungs and 1,000 times more bacteria were found within the blood that spread infection to the liver, and thus, resulted in an increased number of deaths, according to the aforementioned materials.

Closer observation of the cells in the bone marrow and the blood, conducted by Alexandra Bettina, a PhD student in Mehrad’s lab, found that the number of monocytes in the bone marrow and the blood was unaffected in the absence of M-CSF, yet, the cell number was dramatically reduced in the lung. This key observation led to a new hypothesis: despite a lack of cytokine, cells were still being made; however, they were not able to survive in the lungs to perform their jobs effectively, according to Mehrad. M-CSF is needed for the expansion of lung mononuclear phagocytes, tissues that deal with immunological challenges such as infection but were unable to recruit enough leukocytes—cells that work to counteract foreign substances and disease—to the lungs, according to the study.

Mehrad likens the cells to soldiers assembling to get ready to fight, explaining that even though the right number of cells are being made and they are traveling correctly through the blood, once they get to the lung where the infection is, they are not good enough to combat it.

Mehrad aims to make the cells strong enough to battle the infection in the future. According to Mehrad, the knowledge that removal of M-CSF worsens the infection raises questions when it comes to the right amount of M-CSF in therapy. He says, “It may be that during infection, the body is making the right amount of M-CSF and if we add extra, it won’t improve outcomes further. 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.” He also notes that people with weakened immune systems might not make enough M-CSF to fight the infection. He says, “If that’s the case, you could augment that and improve their ability to fight the infection.”