Activation of immune cells against pathogenic stimuli hinges on an evolutionarily conserved cellular protein


03 May 2018

Activation of immune cells against pathogenic stimuli hinges on an evolutionarily conserved cellular protein

 

By Dr. Amit Tuli, Intermediate Fellow

CSIR-Institute of Microbial Technology (IMTECH), Chandigarh

A functional immune system enables our vulnerable bodies to mingle freely with the environment teeming with billions of microbes. Nothing supports this statement better than diseases resulting in severe immunodeficiency where even a brief exposure to “normal” surroundings can be life threatening. Crucial defenders in our immune system army, macrophages (derived from the Greek word meaning “large eaters”) are cells that engulf and degrade pathogens while alerting the other sentinels about the presence of foreign pathogens. Although required for proper immune function, unregulated activation of macrophages is responsible for inflammation associated with several diseases, including cancer and autoimmune disorders.

In a recent study, we have uncovered a molecular player important for macrophage function – Arl11, a protein that activates macrophages in response to pathogenic stimuli (Arya SB et al., Journal of Biological Chemistry, 2018). Our study provides the first clue to the cellular function of Arl11, an evolutionarily conserved protein that has remained functionally uncharacterized till date. Our research findings show that Arl11 expression is up-regulated in macrophages stimulated with pathogen-associated molecules, such as LPS.  Arl11, in turn initiates a cascade of signaling events, resulting in an “effector” response by the activated macrophages to clear away the pathogen. In agreement with this, macrophages lacking Arl11 expression, fail to efficiently internalize, and degrade pathogenic bacteria. Interestingly, we found that merely increasing Arl11 levels was sufficient to induce macrophage activation in the absence of pathogenic stimuli. This suggests Arl11 expression is tightly controlled to prevent unnecessary macrophage activation. Since macrophage activation is not only crucial for defense against pathogens, but also leads to inflammation that damages the uninfected normal tissues. Therefore, it will be highly relevant to further investigate whether Arl11 expression is correlated with inflammatory conditions such as autoimmune disorders, atherosclerosis, and obesity.

Reference:

Arl11 regulates lipopolysacchride-stimulated macrophage activation by promoting MAPK signaling. Subhash B. Arya, Gaurav Kumar, Harmeet Kaur, Amandeep Kaur, and Amit Tuli. Journal of Biological Chemistry. April 2018

Banner image credit: Dr. Amit Tuli. Description:Arl11 is a nucleo-cytoplasmic protein and colocalizes with ERK at cortical actin structures. The image shows HeLa cells co-transfected with Arl11 (stained in green) and ERK2 (stained in red), and the actin cytoskeleton is stained with phalloidin (blue).