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Microbes & Immunity Host receptors in immunogenic cell death

and amplifies inflammation. The distinct mechanisms of provide a valuable repository of targets with therapeutic
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immunogenic cell death not only facilitate the elimination potential.
of infected cells but also significantly contribute to New insights into these dynamic host-pathogen
training subsequent adaptive immune responses. Recent interactions are unfolding, shedding light on immune
studies have identified novel immunogenic cell death defense mechanisms and pathogen evasion tactics. It
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pathways, for instance, ferroptosis, which is linked to becomes evident that the host’s ability to initiate various
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redox biology, metabolism, and various diseases. forms of cell death is a critical factor in the outcome of
Despite an incomplete understanding of its regulatory
networks, significant progress has been made in infections. The ongoing discovery of novel receptors,
signaling pathways, and microbial evasion tactics deepens
developing pharmacological tools to target ferroptosis in our understanding of the immune system’s complexity
infectious disease treatment and prevention. 150,151 Deeper and adaptability. Future research should delve deeper
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dissection into the molecules participating in these
signaling awaits further investigation. Yet, pathogens into these complex molecular mechanisms, potentially
exhibit remarkable adaptability through the evolution of revealing novel therapeutic targets for emerging infectious
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complex strategies to circumvent host immune defenses. diseases. Understanding how pathogens modulate
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This is achieved either by direct interference with pivotal immunogenic cell death pathways might pave the way
elements within immunogenic cell death pathways or to the development of innovative immune response
by impeding the functionality of critical components strategies, improving the efficacy of treatments against
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necessary for the induction of inflammation. The various infectious agents. Overall, further studying the
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primary objective of these microorganisms is to alter host diverse mechanisms of immunogenic cell death triggered
cellular environments to enhance their own survival and by pathogen infections is a multidisciplinary endeavor that
proliferation. Consequently, elucidating the molecular has far-reaching implications for medicine, public health,
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mechanisms underlying these interactions offers and our understanding of human biology.
significant potential for developing novel approaches to Acknowledgments
combat infectious diseases.
Immunogenic cell death in response to pathogenic We thank Dr. Shifan Chen from the University of
invasion is a double-edged sword. On the one hand, Connecticut for critical reading of the manuscript and
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cell death represents a defense mechanism that efficiently insights.
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clears infected cells to limit pathogen spread. On the Funding
other hand, excess inflammation causes damage to the
mucosal barrier and tissues, an opportunity that can be The study was supported by the National Natural Science
exploited by infectious microbes. In addition, certain Foundation of China (32272619 to X. S.). The funders had
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pathogens have developed strategies to inhibit cell death, no role in study design, data collection, interpretation, or
thereby enhancing their survival within the host. This the decision to submit the work for publication.
tug-of-war between cell death induction and inhibition
mirrors the evolutionary battle between host defenses Conflict of interest
and microbial virulence. Although apoptosis is the The authors declare that they have no known competing
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most extensively studied type of cell death, the roles of financial interests or personal relationships that could have
pyroptosis and necrosis in immune responses demonstrate appeared to influence the work reported in this paper.
the host’s ability to utilize diverse cell death mechanisms
to combat infections. Recent research has uncovered Author contributions
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PANoptosis, a unique form of inflammatory programmed Conceptualization: Chuang Li, Xiaolong Shao
cell death regulated by PANoptosome complexes, which Visualization: Chuang Li
integrate elements from various cell death pathways. Writing – original draft: All authors
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PANoptosis has distinct biological effects not explained Writing – review & editing: All authors
by other pathways alone, but a better understanding
of the activation and regulation of PANoptosis has Ethics approval and consent to participate
shown great potential for its implications in disease and
future therapeutic strategies. Further investigation is Not applicable.
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encouraged to elucidate hitherto unidentified pathways of Consent for publication
cell death signaling. The identification of novel molecules
implicated in immunogenic cell death is anticipated to Not applicable.

Volume 1 Issue 2 (2024) 38 doi: 10.36922/mi.4264