Interferon-gamma (IFN-γ): Exploring its implications in infectious diseases

Abstract

A key player in driving cellular immunity, IFN-γ is capable of orchestrating numerous protective functions to heighten immune responses in infections and cancers. It can exhibit its immunomodulatory effects by enhancing antigen processing and presentation, increasing leukocyte trafficking, inducing an anti-viral state, boosting the anti-microbial functions and affecting cellular proliferation and apoptosis. A complex interplay between immune cell activity and IFN-γ through coordinated integration of signals from other pathways involving cytokines and Pattern Recognition Receptors (PRRs) such as Interleukin (IL)-4, TNF-α, Lipopolysaccharide (LPS), Type-I Interferons (IFNS) etc. leads to initiation of a cascade of pro-inflammatory responses. Microarray data has unraveled numerous genes whose transcriptional regulation is influenced by IFN-γ. Consequently, IFN-γ stimulated cells display altered expression of many such target genes which mediate its downstream effector functions. The importance of IFN-γ is further reinforced by the fact that mice possessing disruptions in the IFN-γ gene or its receptor develop extreme susceptibility to infectious diseases and rapidly succumb to them. In this review, we attempt to elucidate the biological functions and physiological importance of this versatile cytokine. The functional implications of its biological activity in several infectious diseases and autoimmune pathologies are also discussed. As a counter strategy, many virulent pathogenic species have devised ways to thwart IFN-γ endowed immune-protection. Thus, IFN-γ mediated host-pathogen interactions are critical for our understanding of disease mechanisms and these aspects also manifest enormous therapeutic importance for the annulment of various infections and autoimmune conditions.

Epithelium intrinsic vitamin A signaling co-ordinates pathogen clearance in the gut via IL-18

“…Mice with distinct microbiome compositions were found to be differentially susceptible to Salmonella ; a function of the IFNγ induction by these communities [2]. Mechanistically, IFNγ promotes phagocytosis, oxidative/nitrosative response and cellular autophagy to clear the pathogen [29, 30]. To assess if the defect in IFNγ production was responsible for the increased susceptibility in stop ΔIEC mice, we performed IFNγ feedback experiments (Fig 2E).…”

ADAP Promotes Degranulation and Migration of NK Cells Primed During in vivo Listeria monocytogenes Infection in Mice

“…In addition to their inherent cytotoxic function, NK cells exhibit the capacity to produce effector cytokines and chemokines (19,20), with IFNγ being the principal NK cell cytokine produced early on during infections (21,22). IFN-γ plays a central role for the activation of other immune cells needed for effective immunity to pathogens (23,24). Thus, NK cells act as important immune regulators during infection and inflammation (25).…”

Regulation of Interferon-γ receptor (IFN-γR) expression in macrophages during Mycobacterium tuberculosis infection

“…In summary, IFN-γR downregulation on the macrophage surface favors the pathogen by limiting the role of extrinsic IFN-γ. This may be an important immune evasive mechanism to thwart the very many protective benefits of this pleiotropic cytokine [24]. A deeper understanding of the specific signals and processes that regulate this and the mechanisms thereof, such as the role of second messengers and small RNAs would increase our understanding of this host-pathogen interaction more critically.…”