Monteith Lab tracks immune response
Assistant Professor Andrew Monteith’s lab in the Department of Microbiology is documenting how key immune cells detect infection and how that fails to happen in people with lupus.
Research Associate Ashley Wise led a study focused on neutrophils, the most abundant type of immune cell, and how their mitochondria function as sensory organelles to detect lactate released by bacteria such as Staphylococcus aureus.
“If I were to ask what the role of mitochondria is, most people would respond with them being ‘the powerhouse of the cell.’ However, in neutrophils that is not the case,” Monteith explained. “Rather than letting the bacteria continue to replicate, the mitochondria sense bacterial metabolites in the phagosome and trigger the neutrophil to undergo NETosis—an antimicrobial cell death process—that removes the bacteria from the intracellular niche.”
“We also collaborated with the University of Tennessee Medical Center (UTMC) to identify that neutrophils from people with the autoimmune disease systemic lupus erythematosus (SLE) are incapable of detecting bacterial lactate through their mitochondria,” he said. “As a result, they cannot undergo NETosis when appropriate, which explains why this patient population experiences more frequent and severe bacterial infections.”
Their research appears in the March 12 issue of Cell Host & Microbe, in an article titled, “Mitochondria sense bacterial lactate and drive release of neutrophil extracellular traps.”
Five UT undergraduates also made substantial contributions to the paper, Sarah McDaniel, Ellie Mennen, Eva Belevska, Madalyne Marshall, and Nicole Vaccaro.
Monteith had a history of studying SLE when he joined UT in 2023 and was interested in opportunities to translate the findings to human patients. He met with Jeffry Bieber, a rheumatologist and chief of the division of rheumatology at UTMC.
Monteith said the success of their collaboration was part of the inspiration for starting the Community of Scholars for Immunology and Inflammation (CoSI2), part of the Office of Research, Innovation and Economic Development.
“The collaboration has been excellent, and we hope to have some exciting new data in future,” Monteith said.
Projects underway in his lab are seeking to understand the processes that dictate NETosis, as well as how neutrophils in SLE patients respond in ways that exacerbate inflammation.
“In addition,” Monteith said, “the graduate students in my lab are taking a slightly different approach and trying to understand how metabolic diseases like diabetes and obesity dysregulate neutrophils and leave these patient population more susceptible to bacterial infection.”
By Amy Beth Miller