Zooming in on common immune evasion mechanisms of pathogens in phagolysosomes: potential broad-spectrum therapeutic targets against infectious diseases

• Published in: FEMS microbiology reviews Vol. 47; no. 1; pp. 1 - 18
• Main Authors: Selvapandiyan, Angamuthu, Puri, Niti, Kumar, Pankaj, Alam, Anwar, Ehtesham, Nasreen Zafar, Griffin, George, Hasnain, Seyed Ehtesham
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.01.2023
• Subjects: Acidification; Agonists; Antigen presentation; Antigens; Apoptosis; Autophagy; BCG; BCG vaccines; Communicable diseases; Communicable Diseases - metabolism; Cytosol; Development and progression; Drug development; Health aspects; Humans; Immune Evasion; Immune system; Infectious diseases; Inflammation; Inflammatory response; Intracellular; Lymphocytes T; Macrophages - metabolism; Macrophages - microbiology; Parasitic diseases; Pathogenic microorganisms; Pathogens; Phagocytosis; Phagolysosomes; Phagosomes; Phagosomes - metabolism; Phagosomes - microbiology; Reactive oxygen species; Therapeutic applications; Therapeutic targets; Zooming; India; apoptosis; agonist; phagosomes; antagonist; drug target; intracellular pathogens
• ISSN: 1574-6976; 0168-6445; 1574-6976
• DOI: 10.1093/femsre/fuac041

Abstract The intracellular viral, bacterial, or parasitic pathogens evade the host immune challenges to propagate and cause fatal diseases. The microbes overpower host immunity at various levels including during entry into host cells, phagosome formation, phagosome maturation, phagosome–lysosome fusion forming phagolysosomes, acidification of phagolysosomes, and at times after escape into the cytosol. Phagolysosome is the final organelle in the phagocyte with sophisticated mechanisms to degrade the pathogens. The immune evasion strategies by the pathogens include the arrest of host cell apoptosis, decrease in reactive oxygen species, the elevation of Th2 anti-inflammatory response, avoidance of autophagy and antigen cross-presentation pathways, and escape from phagolysosomal killing. Since the phagolysosome organelle in relation to infection/cure is seldom discussed in the literature, we summarize here the common host as well as pathogen targets manipulated or utilized by the pathogens established in phagosomes and phagolysosomes, to hijack the host immune system for their benefit. These common molecules or pathways can be broad-spectrum therapeutic targets for drug development for intervention against infectious diseases caused by different intracellular pathogens. Broad-spectrum therapeutic phagolysosomal targets against various types of pathogens and the available therapeicstics.