Functional aspects, phenotypic heterogeneity, and tissue immune response of macrophages in infectious diseases

de Sousa, Jorge Rodrigues; Da Costa Vasconcelos, Pedro Fernando; Quaresma, Juarez Antonio Simões

it TBK1/IKKε complex formation, IRF3 and 7 phosphorylation, and NF-κB activation. In the response by IFN-type 1, NSEN of DENV and WNV inhibited activation of JAK1/TYR2. HCV NS5A inhibits activation of STAT1 and 2. Among various immune escape mechanisms, autophagy is critical for flavivirus to mediate biogenesis of viral replication, mainly because of changes in pH and endocytosis. In this sequence, it is worth noting that NS2B and NS4A/B proteins can manipulate autophagy to alter membrane curvature in the Golgi apparatus to facilitate viral replication. However, in another follow-up, NS2B/3 cleaves FAM134B into endoplasmic reticulum (ER) to suppress autophagolysosome formation and reticulophage, a form of selective autophagy, to facilitate viral replication. As a result, NS4A induces cells to produce PIK3, which impair the conversion of LC3I to LC3II and inhibit autophagy. NS2B, NS4A, and NS4B. [215] [216] [217] Interestingly, at the beginning of the infection, both NS4A and NS4B manipulate the cell to mediate membrane curvature and induce autophagy. This process mobilizes the membranes and lipids to establish a proviral event that facilitates viral replication. This directly impacts regulation of the Golgi apparatus because NS2B/3 induces the production of proteases that trigger the cleavage of FAM134B, one of the main receptors involved in endoplasmic reticulum (ER)phagy. 218 Finally, it is worth mentioning that in this dynamic, NS4A can deregulate the PI3K pathway, which, in turn, impairs the conversion of the LC3-I protein to LC3-II ( Figure 4) . 215, 219 Tissue response of macrophages to infectious agents