A mysterious protein produced by a wide spectrum of living things is crucial in regulating the immune response to the most common form of pneumonia, a new Yale School of Medicine study shows. The study appears online in Cell Host & Microbe and in the July 19 print issue.
The protein — present in the blood of every human being – is crucial to a successful immune system response to the bacteria and also seems to prevent that response from damaging the host, according to the researchers.
“We believe this may be a major cornerstone in our understanding how we respond to many different kinds of pathogens,” said Dr. Jack A. Elias, chair of the Department of Internal Medicine and senior author of the paper.
The Yale team investigated the protein, which has a number of names including chitinase 3-like-1 (Chi3l1), because it is a member of an ancient family of proteins found in species as diverse as plants, insects, and humans. This evolutionary conservation led researchers to believe that Chi3l1 plays an essential role in these organisms. However little was known about the functions of this protein in health or disease.
The Yale team found that when mice lacking this key protein were exposed to Streptococcus pneumoniae, they experienced exaggerated levels of inflammation, suffered much greater damage from inflammation and hemorrhage, and had a higher rate of mortality and sepsis (blood poisoning) than those with the protein. They found that the protein helped immune system cells called macrophages to clear the pathogens from the body.
They also found that Chi311 inhibited the innate immune response and decreased its ability to damage tissue in the host. The latter is particularly important, note the researchers, because an overwhelming innate immune system response contributes to the adverse consequences of infections, such as respiratory failure and sepsis, which are among the highest causes of death in hospitals.
“In recent years there has been a much greater appreciation that the perfect immune system response is one that eliminates bacteria but does not kill the host,” said Dr. Charles Dela Cruz, assistant professor of medicine and lead author of the paper. “This molecule seems to help the organism achieve that balance.”
The research was funded by a Parker Francis Fellowship, Flight Attendant Medical Research Institute (FAMRI) Award and NIH KO8 (Dela Cruz). Elias was supported by FAMRI and NIH grants R01-HL-093017 and U01-HL-108638.
Other authors include Wei Liu, Chuan Hua He, Adam Jacoby, Alex Gornitzky, Bing Ma, Richard Flavell, and Chun Geun Lee.