Nikunj Tandel

Amongst several studies, a collection of work mainly focusses about the modulation and signalling pathways of immune system engages during the pathogen exposure and chronic infection. Hence, study understanding the immune profile of individuals living in endemic area of infectious diseases (DOI: 10.3389/fimmu.2025.1547854) depicts that repeated exposure of the pathogen could alter the immunity and generated "memory/trained" immune sentinels is a double-edged sword for the host. It mimics the conditions which is possibly find in the infectious-setting region, where low-grade infection persists despite of the active immune system.Similarly, another work on sepsis-induced immunosuppression (DOI: 10.3389/fimmu.2025.1577105) detailed about the progression of the infection and paralysing the immune system due to impaired antigen presentation, alteration in T-cell function. The latter led to the secondary infection resulting in the vulnerability. These observations point out that outcome of infection not only rely on the first/initial pathogen encounter and its clearance but also depends upon the role of functions of the immune responses. This highlights the importance of monitoring the immune system even after the phase of infection, as 37 immune responses continue to evolve. 38Several studies investigated the reprogramming of host responses due to pathogen 40 exposure and chronic infections in this collection. First study evaluated the immune profiles of 41 individuals residing in the regions (DOI: 42 10. 3389/fimmu.2025.1547854). This work demonstrated that continuous or repeated pathogen 43 exposure can alter the immune cells of immune system, begetting the partial 44 "trained/memorized" immune status. This could be sword having the double edge that affects 45 both susceptibility and severity of diseases. This finding aligns with broader observations in 46 endemic infectious-disease contexts, where immune phenotypes represent an equilibrium 47 between protection and low-grade chronic inflammation. 48Another study addressed oral lichen planus (DOI: 10.3389/fimmu.2025.1553963), a chronic 49 inflammatory mucosal disease whose pathogenesis is under-explored. By using single-cell 50 RNA sequencing, SFRP2 + fibroblasts identified as the origin of inflammatory fibroblasts in the 51 lesion and specifically expressed Wnt5a on a subset of these cells and associated with antigen 52 processing and presentation pathways. Also, SFRP2 + Wnt5a + fibroblasts were found to amplify 53 and maintain local immune inflammation through close interactions with CD8 + T cells and 54 epithelial cells. Also, this study showed the upregulation of pro-inflammatory and antigen-55 presentation-associated molecules, including CXCL12, CXCL14, HLA-A, HLA-B, HLA-C, 56 and ERAP2, in the oral lichen planus samples. Collectively, these observations suggested not 57 to consider fibroblasts as merely structural cells in this disease. And accounts as an important 58 cell which shapes the inflammatory microenvironment to help sustain the chronic immune 59 activation. 60There have been submissions in this collection demonstrating mechanism(s) of infectious and 62 autoimmune diseases. Article addressing the intersection of influenza infection and 63 autoimmunity (DOI: 10.3389/fimmu.2025.1558386) to investigates the role of viral insults that 64 may initiate or exacerbate autoimmune signalling, through the several approaches of molecular 65 mimicry, bystander activation, or tissue-specific inflammation. This study highlights that 66 occurrence of autoimmune phenomena in many cases may not trigger in isolation but arises 67 due the involvement of multifactorial signalling cascades of immune sentinels and inherent 68 host susceptibility. Furthermore, an article on thymosin-α1 discuss its role in modulating immune-inflammatory 83 responses (DOI: 10.3389/fimmu.2025.1571456) that selective immunomodulation may aid in 84 controlling excessive inflammation during maintaining protective immunity in the critical-care 85 and post-infection scenario. In nutshell, the efficacy of immunomodulation in any 86 infectious/pathogenic condition mainly relies on respective diseases context or the resulted 87 microenvironment wherein vivid immune sentinels have defined role, and not depends upon 88 immunosuppressive or stimulatory approaches. Further, combining immunological readout, 89 alongside multi-omics data and longitudinal studies can help in revealing the pattern of immune 90 response over the time and disease pathogenicity. Simultaneously, currently in experimental 91 phase of machine learning and AI integration may advisable in identifying a disease-specific 92 immune signature for the development of personalized drug therapeutics. 93This research topic compiles a numerous study to help us better understand how does immune 95 system work, especially during the infectious and inflammatory conditions. Thorough 96 observation from clinical, systemic, and mechanistic point-of-view of an infection emphasizes 97 the complexity of immune system and the specialized role of distinct immune cell niches. 98Connecting these dots can help bridge the gap between basic and translational research while 99 aligning them with clinical practice on a uniform platform. Furthermore, insights gained form 100 experimental studies and real-world longitudinal data can strengthen health care system by 101 enabling the development of improved diagnostic tools, target specific therapeutics, and 102 effective prevention strategies. Overall, in today's AI world, a deeper understanding of the

Tandel N, et al. Immune Netw. 2026 Aug;26(4):e34. https://doi.org/10.4110/in.2026.26.e34

Genetic variant(s) of concern (VoC) of SARS-CoV-2 have been emerging worldwide due to mutations in the gene encoding spike glycoprotein. We performed comprehensive analyses of spike protein mutations in the significant variant clade of SARS-CoV-2, using the data available on the Nextstrain server. We selected various mutations, namely, A222V, N439K, N501Y, L452R, Y453F, E484K, K417N, T478K, L981F, L212I, N856K, T547K, G496S, and Y369C for this study. These mutations were chosen based on their global entropic score, emergence, spread, transmission, and their location in the spike receptor binding domain (RBD). The relative abundance of these mutations was mapped with global mutation D614G as a reference. Our analyses suggest the rapid emergence of newer global mutations alongside D614G, as reported during the recent waves of COVID-19 in various parts of the world. These mutations could be instrumentally imperative for the transmission, infectivity, virulence, and host immune system’s evasion of SARS-CoV-2. The probable impact of these mutations on vaccine effectiveness, antigenic diversity, antibody interactions, protein stability, RBD flexibility, and accessibility to human cell receptor ACE2 was studied in silico. Overall, the present study can help researchers to design the next generation of vaccines and biotherapeutics to combat COVID-19 infection.

Open access peer-reviewed chapter

The innate lymphoid cell (ILC) system comprising of the circulating and tissue-resident cells is known to clear infectious pathogens, establish immune homeostasis as well as confer antitumor immunity. Human natural killer cells (hNKs) and other ILCs carry out mopping of the infectious pathogens and perform cytolytic activity regulated by the non-adaptive immune system. The NK cells generate immunological memory and rapid recall response tightly regulated by the adaptive immunity. The interaction of NK and B cell, and its role to induce the pathogen specific immunity is not fully understood. Hence, present article sheds light on the interaction between NK and B cells and resulting immune responses in the infectious diseases. The immune responses elicited by the NK-B cell interaction is of particular importance for developing therapeutic vaccines against the infectious pathogens. Further, experimental evidences suggest the immune-response driven by NK cell population elicits the host-specific antibodies and memory B cells. Also, recently developed humanized immune system (HIS) mice and their importance in to understanding the NK-B cell interaction and resulting pathogen specific immunity has been discussed. Graphical Abstract

Crohn’s disease and ulcerative colitis, two major forms of inflammatory bowel disease (IBD) in humans, afflicted in genetically predisposed individuals due to dysregulated immune response directed against constituents of gut flora. The defective immune responses mounted against the regulatory mechanisms amplify and maintain the IBD-induced mucosal inflammation. Therefore, restoring the balance between inflammatory and anti-inflammatory immunepathways in the gut may contribute to halting the IBD-associated tissue-damaging immune response. Phenotypic and functional characterization of various immune-suppressive T cells (regulatory T cells; Tregs) over the last decade has been used to optimize the procedures for in vitro expansion of these cells for developing therapeutic interventional strategies. In this paper, we review the mechanisms of action and functional importance of Tregs during the pathogenesis of IBD and modulating the disease induced inflammation as well as role of mouse models including humanized mice repopulated with the human immune system (HIS) to study the IBD. “Humanized” mouse models provide new tools to analyze human Treg ontogeny, immunobiology, and therapy and the role of Tregs in developing interventional strategies against IBD. Overall, humanized mouse models replicate the human conditions and prove a viable tool to study molecular functions of human Tregs to harness their therapeutic potential.

Among the numerous infectious diseases, malaria still remains the main cause of morbidity and mortality across the world. Every year more than 200 million cases are registered and death toll is of around 4,00,000. The emergence of insecticide and drug resistance has surged an alarming situation to find an effective means to tackle it. From various approaches used for reducing the damage created by malaria to the society, developing effective vaccine has gained the attention of scientific community. The large genome size (24 MB), heterogeneity of the genes, complex life cycle in two different hosts, and expression of wide range of these genes are claimed to hinder the malaria vaccine development. It requires good understanding of the host-pathogen interaction and its correlation with the sterile protection. Recently, subunit vaccine have shown certain promising responses; however, the currently in use of RTS,S vaccine has failed to generate the long-term sterile protection as well as effector memory CD8+T cells. However, the success of sterile protection through vaccination has been proven long back by experimental approaches, where it could be achieved using irradiated sporozoites (RAS) in rodents and humans. Similarly, GAP (genetically attenuated parasite) and CPS (chloroquine chemoprophylaxis with Plasmodium sporozoites) have been shown to induce sterile immunity. Despite all the developments, generation of species and stage specific-CD8+ T cell responses has been modest. In order to generate long-lasting immune response, particularly, liver-stage specific-CD8+ T cells, it is indeed required to study the CD8+ T cell epitope repertoire and its implications on the host immune system. In this chapter we will discuss the current status of T cell-based vaccines and the challenges associated with it.

Transdermal immunization exhibits poor immunogenic responses due to poor permeability of antigens through the skin. Elastic liposomes, the ultradeformable nanoscale lipid vesicles, overcome the permeability issues and prove a versatile nanocarrier for transcutaneous delivery of protein, peptide, and nucleic acid antigens. Elastic liposome-mediated subcutaneous delivery of chimeric fusion protein (PfMSP-Fu₂₄) of Plasmodium falciparum exhibited improved immunogenic responses. Elastic liposomes-mediated immunization of PfMSP-Fu₂₄ conferred immunity to the asexual blood-stage infection. Present study is an attempt to compare the protective immune response mounted by the PfMSP-Fu₂₄ upon administered through transdermal and intramuscular routes. Humoral and cell-mediated immune (CMI) response elicited by topical and intramuscularly administered PfMSP-Fu₂₄-laden elastic liposomes (EL-PfMSP-Fu₂₄) were compared and normalized with the vehicle control. Sizeable immune responses were seen with the transcutaneously immunized EL-PfMSP-Fu₂₄ and compared with those elicited with intramuscularly administered antigen. Our results show significant IgG isotype subclass (IgG1and IgG3) response of specific antibody levels as well as cell-mediated immunity (CMI) activating factor (IFN-γ), a crucial player in conferring resistance to blood-stage malaria in mice receiving EL-PfMSP-Fu₂₄ through transdermal route as compared to the intramuscularly administered formulation. Heightened immune response obtained by the vaccination of EL-PfMSP-Fu₂₄ was complemented by the quantification of the transcript (mRNA) levels cell-mediated (IFN-γ, IL-4), and regulatory immune response (IL-10) in the lymph nodes and spleen. Collectively, elastic liposomes prove their immune-adjuvant property as they evoke sizeable and perdurable immune response against PfMSP-Fu₂₄ and justify its potential for the improved vaccine delivery to inducing both humoral and CM immune response.

Introduction: Tuberculosis (TB) is still one of the major global health threats and delayed diagnosis or misdiagnosis continues to fuel the global epidemic. The conventional diagnostic approaches have shortcomings that might hinder the process of diagnosis of the disease and ultimately affect the prognosis. Area Covered: We emphasize on the process of the synthesis of liposomes, its physicochemical properties affecting the formulation and their utilization in the field of molecular diagnostics for TB. The review also sheds a light on other nanoparticle-based molecular diagnostic approaches for TB. Despite the advent of science, we are yet to have a diagnostic tool that is simple, rapid, sensitive, and specific, and most importantly, one that enables us to demarcate patients with active tuberculosis from those with quiescent lesions, prior vaccination, or other diseases. Expert opinion: The utility of liposomes for diagnostic purposes has been attempted so as to overcome the challenges posed by conventional diagnostic tools for Tuberculosis. Through this review we present insights into liposome formulation and selection processes, various studies that report the use of liposome-based diagnostic tools for tuberculosis, as well as the limitations associated with the same that can be improvised to make the technology more efficient.