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

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 Ca2+ 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.

Why Does SARS-CoV-2 Infection Induce Autoantibody Production?

SARS-CoV-2 infection induces the production of autoantibodies, which is significantly associated with complications during hospitalization and a more severe prognosis in COVID-19 patients. Such a response of the patient's immune system may reflect (1) the dysregulation of the immune response or (2) it may be an attempt to regulate itself in situations where the non-infectious self poses a greater threat than the infectious non-self. Of significance may be the primary virus-host cell interaction where the surface-bound ACE2 ectoenzyme plays a critical role. Here, we present a brief analysis of recent findings concerning the immune recognition of SARS-CoV-2, which, we believe, favors the second possibility as the underlying reason for the production of autoantibodies during COVID-19.