Two innate immune functions cooperate to fight infection
Any gourmand will tell you that putting food in your mouth and digesting it are important functions of the process known as "eating."
In the cell, two similar functions– phagocytosis and autophagy – are both involved in innate immunity, and researchers led by those at Baylor College of Medicine said they now better understand how the two are linked to boost protection against disease.
Protecting against disease
Nuclear factor-like 2 transcription factor is the key to the two activities, said Dr. N. Tony Eissa, professor of medicine – pulmonary at BCM and corresponding author of the report that appears online in the journal Immunity. Researchers from The University of Texas Medical School at Houston and Tokyo Metropolitan Institute of Medical Science in Japan also took part in this work.
Phagocytosis is the engulfing of invading bacteria or other cellular debris by phagocytes – cells that develop for this purpose. Autophagy is literally "self-eating" or, in this case, the degradation of cells or cell debris.
When Eissa and his colleagues infected mice that lacked genes critical to autophagy with forms of mycobacteria (the family that includes the organism that causes tuberculosis), they found that the macrophages (cells that perform phagocytosis) were grabbing or engulfing more than they could handle.
"They took in so much stuff, and they could not kill it," he said.
In the absence of autophagy, the macrophages had too many of two specific scavenger receptors – macrophage receptor with collagenous structure and macrophage scavenger receptor 1.
Nuclear factor-like 2 transcription factor allows the scavenger receptors to be active.
"We are figuring out how to use this in a clinical infectious disease such as tuberculosis," said Eissa. "We want to ensure that autophagy is not deficient and the body doesn’t end up ‘eating" more than it can digest."
"The big finding in this paper is that autophagy controls both processes," he said.
Others who took part in this research include Diana L. Bonilla, Abhisek Bhattacharya, Youbao Sha, Yi Xu and Qian Xiang, all of BCM; Arshad Kan and Chinnaswamy Jagannath of UT Medical School at Houston; and Masaaki Komatsu of Tokyo Metropolitan Institute of Medical Science in Japan.
Funding and support for this work came from the National Institutes of Health, The National Heart, Lung and Blood Institute, National Institute of Allergy and Infectious Diseases, the American Heart Association, the Cytometry and Cell Sorting Core at Baylor College of Medicine with funding from the National Institutes of Health (NIAID P30AI036211, NCI P30CA125123, and NCR S10RR024574).