Innate Immune Recognition, Integrated Stress Response, Infection, and Tumorigenesis

SIMPLE SUMMARY: The cellular and humoral mechanisms of natural immunity are at the beginning of all the defence processes of an organism. Their defence function is based on the ability to recognize pathogen-associated molecular patterns and damage (danger)-associated molecular patterns using pattern recognition receptors. Recognition of pathogen-associated molecular patterns and/or damage (danger)-associated molecular patterns has a crucial role in the activation of the innate immune defence mechanisms. An inflammatory response, as a basic event in early defence occurs, which is the complex, developmentally acquired ability of living organisms to react to various damages. If it is not strictly regulated, it turns into damaging inflammation. This is common both in some infectious diseases, such as prolonged COVID-19, and in precancerous tissue preceding the development of tumors. This short review presents a vision of an integration of innate immune recognition, cell-autonomous stress response, infection, and tumorigenesis. ABSTRACT: Engagement of PRRs in recognition of PAMPs or DAMPs is one of the processes that initiates cellular stress. These sensors are involved in signaling pathways leading to induction of innate immune processes. Signaling initiated by PRRs is associated with the activation of MyD88-dependent signaling pathways and myddosome formation. MyD88 downstream signaling depends upon the context of signaling initiation, the cell (sub)type and the microenvironment of signal initiation. Recognition of PAMPs or DAMPs through PRRs activates the cellular autonomous defence mechanism, which orchestrates the cell responses to resolve specific insults at the single cell level. In general, stressed endoplasmic reticulum is directly linked with the induction of autophagy and initiation of mitochondrial stress. These processes are regulated by the release of Ca(2+) from ER stores accepted by mitochondria, which respond through membrane depolarization and the production of reactive oxygen species generating signals leading to inflammasome activation. In parallel, signaling from PRRs initiates the accumulation of misfolded or inappropriately post-translationally modified proteins in the ER and triggers a group of conserved emergency rescue pathways known as unfolded protein response. The cell-autonomous effector mechanisms have evolutionarily ancient roots and were gradually specialized for the defence of specific cell (sub)types. All of these processes are common to the innate immune recognition of microbial pathogens and tumorigenesis as well. PRRs are active in both cases. Downstream are activated signaling pathways initiated by myddosomes, translated by the cellular autonomous defence mechanism, and finalized by inflammasomes.