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Microbes & Immunity Host receptors in immunogenic cell death

1. Introduction the activation of inflammasomes and alternative signal
transduction pathways, which culminates in an array of
Immunogenic cell death induced by infections caused by immunogenic cell death phenotypes.
pathogens plays a major role in host immune responses
to eradicate evading bacteria or viruses. Investigation of 2. Host receptors for pathogen component
1
signaling pathways involved in host innate immunity has recognition
revealed the rich and diverse mechanisms that govern the
sensing of immune cells to various ligands, particularly The dynamic interaction between PAMPs and PRRs
pathogen-associated molecular patterns (PAMPs). empowers the host to distinguish self-entities from
2
Upon the recognition of PAMPs, the host germ line- foreign pathogens and to efficiently deter pathogenic
encoded pattern recognition receptors (PRRs) dictate invasions. Despite the immense diversity in the
host antimicrobial responses as well as proinflammatory microbial constitution, the host is nonetheless able to
reactions. Subsequently, PRRs located at the cell surface distinguish them through a small number of receptors
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or intracellularly activate a series of downstream signaling using mechanisms that are strikingly similar yet
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cascades, involving ligands, receptors, adaptor molecules, significantly distinct. Within the PRR family, members
kinases, and transcription factors. The activation of these include Toll-like receptors (TLRs), nucleotide-binding
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signal transduction pathways commands the host to oligomerization domain (NOD)-like receptors (NLRs),
express a wide array of immunoregulatory genes, resulting retinoid acid-inducible gene I (RIG-I)-like receptors
in the synthesis of cytokines and chemokines that recruit (RLRs), and C-type lectin receptors (CLRs). The
2
other activated immune cells to eliminate the invading activation of PRRs typically leads to the assembly of the
pathogen. While the execution of the innate immune inflammasome complex, a crucial sensor and mediator
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response is accomplished by the actions of phagocytes that subsequently triggers the activation of downstream
and antigen-presenting cells, the orchestration of adaptive inflammatory signalings. The forefront of research
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immunity is facilitated by specialized immune cells. This focused on deciphering the complex interactions
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review mainly discusses recent proceedings regarding between hosts and pathogens, identifying novel PAMP-
pathogen-mediated receptor signaling and cell death in PRR interactions as well as the intricate mechanisms
innate immune cells, with an emphasis on macrophages of recognition and the subsequent signaling cascades
3
and dendritic cells. (Figure 1). For instance, the primate-specific protein,
Host antimicrobial responses following the PRR- NLR family pyrin domain-containing protein 11
mediated signaling include proinflammatory reactions and (NLRP11) has been newly identified as a PRR for cytosolic
immunogenic cell death. When inflammation and other lipopolysaccharide (LPS), necessary for activating the
3,7
innate immune responses fail to combat the infection, caspase-4 inflammasome in human macrophages during
infected cells opt to initiate diverse pathways that lead infection by Gram-negative bacteria. 15
to immunogenic cell death. These diverse forms of cell 2.1. Role of Toll-like receptors in immune
1
death play crucial roles in amplifying various downstream surveillance
immune responses, restricting pathogen dissemination, and
eliminating infections. Apoptosis, pyroptosis, necrosis, and Among all PRRs, members of the TLRs family have received
1
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lysosomal cell death, representing the predominant and the most attention from researchers in the past decades.
extensively investigated types of cell death triggered by TLRs were initially identified due to their homology with
8,9
pathogen infections, are discussed in this review. the Drosophila melanogaster Toll protein, which acts as an
immune guarder in the defense against fungal infections.
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Investigating the myriad manifestations of
immunogenic cell death instigated by pathogen infection The observation that Drosophila melanogaster lacking Toll
protein is susceptible to fungal infection contributed to
is pivotal across several scientific domains. Such research the discovery of the importance of Toll protein in other
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provides pivotal insights into the pathophysiology of species. TLRs are expressed on cell membranes of diverse
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infectious diseases, facilitating the formulation of bespoke antigen-presenting cells, including macrophages and
therapeutic and prophylactic approaches. In addition, 19
11
enhanced comprehension of immunogenic cell death dendritic cells. Although ubiquitously expressed in many
mechanisms is instrumental in refining immunization scenarios, specific TLR expression can be inducible and
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strategies and therapeutic modalities to bolster endogenous exclusive to pathogen infections.
immune defenses against pathogenic assaults. This The TLR is composed of an extracellular domain
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review encapsulates the forefront of discoveries in containing the leucine-rich repeat (LRR) motif, and a
delineating PAMPs-recognizing host receptors that trigger Toll/interleukin-1 (receptor [TIR] homology domain
Volume 1 Issue 2 (2024) 30 doi: 10.36922/mi.4264