The infection of COVID-19 is directly linked to the destruction of lung epithelial cells, and the cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes (cGAS-STING) system has been implicated in the pathology of respiratory infections. This study aimed to systematize the relationship between the pathophysiology of COVID-19 and the cGAS-STING system’s activation in the lungs. Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is an RNA virus that belongs to the Coronaviridae family whose genetic material is produced by a single positive RNA molecule (RNA+). The cGAS-STING signaling pathway has emerged as a key mediator of injury caused by infection and cellular or tissue stress. The cGAS-STING cyclic pathway is part of innate immunity and is activated from cytosolic DNA responses present in newly formed syncytia, by cell-to-cell fusion, in target of angiotensin-converting enzyme 2 (ACE2) expression and SARS-CoV-2 Spike protein. Although this pathway is canonically understood to be responsive to both pathogen-derived and host-derived DNA, it has been demonstrated to cross-communicate with the retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs). cGAS-STING activation is significant to interferon production, mainly type-I interferons (IFN-I), in a SARS-CoV-2 infection scenario, indicating a major antiviral role of the cGAS-STING pathway. It was identified that in SARS-CoV-2 the cGAS-STING axis is activated, but the inflammatory response could be specific for nuclear factor-κB (NF-κB) in infected cells, and that this axis is potentiated by a cytokine storm produced by the immune system’s cells.

Tumor necrosis factor receptor (TNFR)-associated factors (TRAFs) are a family of intracellular signaling adaptors that associate with the cytoplasmic tails of a diverse range of lymphocyte receptors, including members of the TNFR superfamily, the Toll-like receptor (TLR)/interleukin-1 (IL-1) receptor superfamily, and the IL-6 receptor family that are major targets for therapeutic intervention for inflammatory diseases. TRAF5 is one of the seven family members of the TRAF family and is highly expressed by B- and T-lymphocytes. As compared to other family members, the biological and pathophysiological functions of TRAF5 have remained ambiguous since its discovery. TRAF5 promotes lymphocyte signaling for the TNFR family molecules such as glucocorticoid-induced TNFR family-related protein (GITR), CD27, and CD40. In contrast, TRAF5 limits the activity of the common signaling receptor subunit glycoprotein 130 kDa (gp130) in CD4⁺ T cells that requires signaling by IL-6 and IL-27. TRAF5 also restrains TLR signaling in B cells. Thus, TRAF5 regulates lymphocyte signaling in both positive and negative ways. This review will summarize the findings of recent studies of TRAF5 in terms of how TRAF5 regulates signaling in lymphocytes and other cell types and how TRAF5 expression contributes to inflammatory and autoimmune diseases in mice and humans.

Coronavirus disease caused by the recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represents a major public health that has submerged the world into a crisis unprecedented in the modern era. A better understanding of the innate immune response could help to fight this pandemic and be better prepared for potential future outbreaks. Interestingly, innate immune cells can develop a non-specific memory termed trained immunity. This review details recent evidence concerning the interaction of SARS-CoV-2 with innate immune cells, in particular those in which the trained immunity activity has been demonstrated.

Human cytomegalovirus (HCMV), whose genome is around 235 kb, is a ubiquitous human herpesvirus that infects between 40% and 95% of the population. Though HCMV infection is commonly asymptomatic and leads to subtle clinical symptoms, it can promote robust immune responses and establish lifelong latency. In addition, in immunocompromised hosts, including individuals with acquired immunodeficiency syndrome (AIDS), transplant recipients, and developing fetuses it can lead to severe diseases. Immunosenescence, well-defined as the alterations in the immune system, is linked mainly to aging and has been recently gathering considerable attention. Senescence was characterized by an elevated inflammation and hence considered a powerful contributor to “inflammaging” that is measured mainly by tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and C-reactive protein (CRP) levels as well as latent viral infections, for instance, cytomegalovirus (CMV). Inflammaging resulted in a senescence-associated secretory phenotype (SASP). HCMV is markedly associated with accelerated aging of the immune system as well as several age-associated diseases that accumulate and subsequently deteriorate the immune responses, thus have been linked to mortality, declined vaccine efficacy, serious diseases, and tumors in the elderly. HCMV triggers or exacerbates immunosenescence; on the other hand, the weakened immune responses and inflammaging favor viral reactivation and highlight the role of HCMV in aging as well as viral-associated tumors. HCMV reactivation resulting in sequential lytic and latent viral cycles could contribute to HCMV genomic variability. Besides the oncomodulatory role and transforming capacities of HCMV, the immune-privileged tumor microenvironment has been considered the main element in tumor progression and aggressiveness. Therefore, the interplay between HCMV, immunosenescence, and cancer will aid in discovering new therapeutic approaches that target HCMV and act as immune response boosters mainly to fight cancers of poor prognosis, particularly in the elderly population.

Immunoinformatics is an emerging area focused on development and applications of methods used to facilitate vaccine development. There is a growing interest in the field of vaccinology centered on the new omic science named ‘vaccinomics’. However, this approach has not succeeded to provide a solution against major infections affecting both animals and humans, since tick vaccines are still being developed based on conventional biochemical or immunological methods to dissect the molecular structure of the pathogen, looking for a candidate antigen. The availability of complete genomes and the novel advanced technologies, such as data mining, bioinformatics, microarrays, and proteomics, have revolutionized the approach to vaccine development and provided a new impulse to tick research. The aim of this review is to explore how modern vaccinology will contribute to the discovery of new candidate antigens and to understand the research process to improve existing vaccines. Under this concept, the omic age of ticks will make it possible to design vaccines starting from a prediction based on the in silico analysis of gene sequences obtained by data mining using computer algorithms, without the need to keep the pathogen growing in vitro. This new genome-based approach has been named “reverse vaccinology 3.0” or “vaccinomics 1.0” and can be applied to ticks.