Read medical school professor Dr. Pukkila-Wally and MD/PhD student Samantha Tsekan
Two recently published studies examining the immune response of C. elegans reveal far-reaching implications for understanding the evolutionary origins of pathogen detection and immunity itself in higher animals.
The study, co-authored by Samantha “Sammy” Tse-Kang, a medical doctoral student, and Reed Pukkila-Walley, MD, PhD, a professor of medicine, shows that host cells sense infection, leading to effector-induced responses in animals. The mechanism of immunity was clarified. It refers to the harmful effects of pathogens, not simply the presence of dangerous microorganisms. New research details the mechanisms by which immune modulators have a conserved role across all organisms in sensing pathogens.
The paper, published simultaneously in the journal Immunity and Cell Reports on September 18, examines a type of immunomodulatory factor called SARM that is required for immune defense in plants and bacteria. It was previously unknown whether these proteins play a role in pathogen sensing in animals. Tse-Kang et al. showed that C. elegans SARM homologues are specifically expressed in the cellular compartment of enterocytes, where they can activate protective immune defenses in response to damage to the host by pathogens.
“As we continued our research, we realized that we were thinking about two separate mechanisms: one that activates the host immune response during infection, and one that follows the same pathway. It is a mechanism that prevents harmful inflammation by suppressing it.
– Read Pukkila Wally, Maryland
Tse-Kang said the two papers started with one question: “What controls the immune response in C. elegans?”
“These related papers started with unbiased genetic screening, but it wasn’t always clear where these stories were going. As we progressed our research, we started to think about two different mechanisms. I realized that one mechanism activates the host’s immune response during infection, and the other prevents damaging inflammation by suppressing the same pathway.” said. “Sammy was essential to this realization and to carrying out an incredibly detailed and challenging experiment.”
“Our study shows that C. elegans intestinal epithelial cells can identify not only the presence of infectious pathogens, but also those that are actively causing disease, by sensing so-called ‘patterns of pathogenesis.’ “We are showing that,” Tsekan said. “We believe this will pave the way for similar studies in higher mammals such as mice and humans.”
Tse-Kang and Pukkila-Worley acknowledge the contributions of former lab member Nick Peterson, MD, PhD’24. In 2023, Dr. Peterson published a paper in Immunity characterizing the different pathogenesis patterns of C. elegans. He and his colleagues showed that metabolites derived from pathogens are sensed within the host and indicate the virulence potential of the invading pathogen.
Dr. Fiachra Humphreys, Assistant Professor of Medicine. Khurshid A. Wani, Lecturer in Medicine. Amanda Page, MD/PhD student; Peterson and Peterson are co-authors with Tse-Kang and Pukkila-Worley of a paper published in the journal Immunity that identifies TIR-1 as a guard protein in effector-driven immune responses.
“There was some luck involved in this, but in science you also need a little luck. The rest was the result of great conversations in the lab where we bounced ideas off each other. These stories are the result of everyone else’s It was a team effort,” said Tsekan.
Tsekan earned a bachelor’s degree from Boston University and worked as a research engineer at MGH, MIT, and Harvard University’s Ragon Institute before joining MIT in 2016. She is the inaugural recipient of the Robert W. Finberg, MD Memorial Research Award. training award and the Ruth L. Kirshstein National Research Service Award from the National Institutes of Health.
She completed her PhD in April and returned to pursue her medical degree in July.
