Damaged Immune Receptor Could Lead to More Severe Comorbidities in HIV, Study Finds

While treatment for HIV has made tremendous strides over the past few decades, many patients with the infection still struggle with comorbidities such as chronic inflammation, diabetes, and cardiovascular problems, among others.

Researchers at Michigan State University sought to understand why patients with HIV develop such complications, in a study recently published in the Journal of Immunology.

Investigators studied the immune systems of both healthy patients and patients with HIV. Within the study, researchers tested patients’ blood by isolating their white blood cells and stimulating them with interferon alpha. The authors identified an immune receptor, SLAMF7, that had the ability to lower or “tone down” the body’s immune response when activated on monocytes.

After stimulating a patient’s white blood cells, researchers examined how SLAMF7 responded and found that it was unresponsive in certain patients with HIV who had more severe complications. However, researchers also noted that SLAMF7 increased the monocytes’ resistance to HIV by raising the level of the CCL3L1 protein, which makes it more difficult for the HIV virus to enter cells.

“When receptors need to turn immune cells on because of an infection, they bind to the cells and work with fellow receptors to activate the immune system. when signs of infection or inflammation go away, the receptors switch gears and turn off the immune response,” said lead study author, Patrick O’Connell, in a statement.

Often, clinicians treating a patient with HIV will find that the patient has malfunctioning receptors and their body isn’t able to shut off their own immune systems, which can leave the body in a chronic proinflammatory state. If there is overactivation, this could lead to autoimmune disorders where the body attacks its own tissues. Conversely, if there is underactivation, the body is unable to fight off infections. “HIV patients are different because they can experience both,” said O’Connell.

Future studies should look to understand the molecular mechanism of the SLAMF7 and the mechanism of action as that could eventually lead to new treatments that target immune activation. “These findings implicate the SLAMF7 receptor as an important regulator of [interferon alpha-driven] innate immune responses during HIV infection,” read the study.

Reference

O'Connell P, Pepelyayeva Y, Blake M, et al. SLAMF7 is a critical negative regulator of IFN-a-mediated CXCL10 production in chronic HIV infection. J Immunol. 2019;202(1):228-238. doi: 10.4049/jimmunol.1800847.