Abstract
Peroxisome proliferator-activated receptor α is a potent regulator of systemic and cellular metabolism and energy homeostasis, but it also suppresses various inflammatory reactions. In this review, we focus on its role in the regulation of innate immunity; in particular, we discuss the PPARα interplay with inflammatory transcription factor signaling, pattern-recognition receptor signaling, and the endocannabinoid system. We also present examples of the PPARα-specific immunomodulatory functions during parasitic, bacterial, and viral infections, as well as approach several issues associated with innate immunity processes, such as the production of reactive nitrogen and oxygen species, phagocytosis, and the effector functions of macrophages, innate lymphoid cells, and mast cells. The described phenomena encourage the application of endogenous and pharmacological PPARα agonists to alleviate the disorders of immunological background and the development of new solutions that engage PPARα activation or suppression.
Highlights
Academic Editors: Manuel Vázquez-Carrera and Walter WahliReceived: 27 August 2021Accepted: 26 September 2021Published: 29 September 2021Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.Innate immunity comprises a sophisticated set of defensive processes, which are evolutionarily very old and originated concomitantly with the development of multicellular organisms
The experiment carried out on the infected mice showed that Peroxisome proliferator-activated receptor α (PPARα) agonist Wy-14643 elevated the expression of M2 macrophage markers, arginase-1, mannose receptor (CD206), Ym1, and TGFβ, and decreased the production of proinflammatory molecules characteristic of the M1 phenotype, such as iNOS, nitric oxide (NO), IL-1β, IL-6 and TNFα [118]. This phenotypic switch was accompanied by a PPARα-dependent increase in phagocytic capacity and efficiency of parasite phagocytosis [118]. These results indicate that PPARα activation might have therapeutic significance, because its immunomodulatory action, on the one hand, strengthens macrophage effector capacity, but, on the other hand, helps to alleviate severe chronic inflammation associated with Chagas disease, which is destructive to various organs
PPARα as a transcription factor exerts a strong impact on cellular metabolism and intracellular signal transduction events, which alters the physiology and behavior of
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Innate immunity comprises a sophisticated set of defensive processes, which are evolutionarily very old and originated concomitantly with the development of multicellular organisms. The defense against invading pathogens is a crucial physiological mechanism that guarantees survival. The development of these mechanisms is a manifestation of a constant race between pathogens (including unicellular pro- and eukaryotic invaders) and host. The biological processes involved in the innate immune response are very complex and tightly regulated on multiple levels, because they may be very harmful when left unsupervised. Peroxisome proliferator-activated receptor α (PPARα) has emerged as an important player in this network, and this review aims to present several aspects of its involvement in the regulation of innate immunity
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
