CONICET | Buscador de Institutos y Recursos Humanos

Viral infectious diseases have a great impact on the humankind. Pandemic, epidemic andendemic viral diseases produce considerably morbidity and mortality negatively affecting not onlyhealth and well-being but also the local and global economy by increasing school and work absenteeismas well as the healthcare systems? expenses. Probably the best example of this global threat is theinfectious disease caused by the novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which has infected millions of people globally during the 2019-2020 pandemic (WHO, coronaviruspandemic; 1). In addition, viral infections also affect human economy by inducing losses in livestockand crops (2). Moreover, viral diseases can break down the barriers between animals and people creatingnew potential dangers to human health (3). The SARS-CoV-2 pandemic pushed healthcare systemsaround the world to the limit and pressured the scientific community to provide solutions that help toprevent or alleviate its harmful effects. In consequence, in the past few months, the work of scientistsactively investigating the biological features of viral infections and the potential preventive andtherapeutic tools to combat them has undoubtedly been revalued.One of the disciplines that has worked and is working actively in the prevention of viralinfections is the Nutritional Immunology (4-7). One of the most important fields of NutritionalImmunology is the study of the relationship between nutrition, immunity and infections. During the lastdecades, incredible advances have been made in understanding how nutrients (or the lack of them)influence the microbiota and the immune system and affect the resistance to viral infections. Scientistshave gain insight into the cellular and molecular interactions of nutrients and microorganisms with theimmune system and this information has allowed the development of practical applications andbiotechnological tools for improving the immune system and ameliorating the negative consequencesof viral infections in humans and animals. Themanuscripts gathered in this Research Topic are examplesof the mechanistic and applied investigations into the effects of nutritional and immunologicalinterventions on viral diseases.The interaction and stimulation of intestinal epithelial cells (IECs) and antigen presenting cells(APCs) in the gastrointestinal mucosa by beneficial immunomodulatory microorganisms has beensuggested as one of the most important mechanisms involved in the improvement of the resistanceagainst viral infections induced by nutritional and immunological interventions with probiotic foods andIn reviewfeeds (1, 4, 8). Therefore, there is great interest in elucidating the mechanisms involved in the interactionbetween beneficial microorganisms with IECs and APCs, which are the first to meet the microbes andtheir molecules reaching the intestinal mucosa. In this Research Topic, Garcia-Castillo et al., Kanmaniand Kim, and Albarracin et al., provide some clues of the cellular and molecular mechanisms involvedin the beneficial interactions of probiotic lactobacilli strains with IECs and APCs. Interestingly,Albarracin et al., demonstrated that the interaction of probiotic lactobacilli such as Lactobacillusrhamnosus CRL1505 or L. plantarum MPL16 with IECs not only influence the antiviral immuneresponse in the gastrointestinal tract but, in addition, may contribute to the beneficial modulation of theinnate antiviral responses in distant mucosal tissues such as the respiratory tract.In addition to studying the probiotic-induced immune changes in the host, it is also necessary tofind out which bacterial molecules are responsible for their beneficial effects. In this regard, Mizuno etal developed a D-alanyl-lipoteichoic acid biosynthesis protein knockout-mutant strain, to demonstratethe key role of lipoteichoic acid in the anti-inflammatory effect induced by the probiotic L. plantarumCRL1506 strain in the context of Toll-like receptor (TLR)-3-mediated intestinal inflammation. Thecharacterization of the immunomodulatory effects of beneficial microorganisms and their effectormolecules on the mucosal immune system provides the scientific basis to apply them for the modulatingboth the innate immunity and the adaptive immunity targeting specific antigens. Thus, microorganismsand immunomodulatory molecules have been proposed as adjuvants for the generation of mucosalvaccines. Raya-Tonetti et al., demonstrated that bacterium-like particles (BLPs) obtained from differentimmunomodulatory lactobacilli strains differed in their abilities to regulate intestinal and systemicadaptive immune responses induced by the oral administration of a rotavirus vaccine. The workproposed that BLPs derived from highly immunomodulatory lactobacilli strain as an excellentalternative for the development of mucosal antiviral vaccines, indicating that it is necessary toappropriately select BLPs to find those with the most efficient adjuvant properties. In addition, Nigarand Shimosato reviewed how unmethylated cytosine?guanine dinucleotide (CpG) motifs and singlestrandedsynthetic oligodeoxynucleotides, acting through TLR9 activation, are potent stimulators of thehost immune response making them an interesting alternative as mucosal adjuvants for antiviral andantitumor vaccines.Nutrients such as micronutrients and flavonoids also have been shown to influence the immuneresponses against viral infections. In this regard, zinc have been shown to regulate diverse physiologicalfunctions and to play crucial, and sometimes divergent roles in viral infections. Kar et al., demonstratedthat zinc depletion inhibited Dengue Virus and Japanese Encephalitis Virus infections in IECs but hadno effect on rotavirus infection. These results pointed out that modulation of zinc homeostasis duringvirus infection could be a component of the host antiviral response. Thus, the modulation of zinchomeostasis could be used as a potent antiviral strategy against flaviviruses. On the other hand, Wu etal., reported that puerarin, an isoflavonoid isolated from traditional Chinese herb Gegen, differentiallymodulates the innate immune response against the Porcine Epidemic Diarrhea Virus. The proteomicstudy performed in this work both in cell cultures and in neonatal pigs demonstrated the ability ofpuerarin to inhibit the virus-induced nuclear factor (NF)-κB activation and inflammatory damage as wellas to increase the expression of several interferon (IFN)-stimulated genes. These two original researcharticles are examples of how Nutritional Immunology applied to viral infections can offer the scientificbasis for the development of new antiviral foods and feeds.On the other hand, it is well known that the adipose tissue plays key roles in immunometabolismin health and in disease conditions such as in viral infections. Therefore, investigating the ability of cellsin the adipose tissue to respond to microbial ligands may contribute to a better understanding of the roleof this physiological system in resistance to infections. It was reported that human and mouse adipocytesare capable of responding to TLR3 activation by producing tumor necrosis factor (TNF)-α, interleukin(IL)-6, IL-8, and chemokine C-C motif ligand (CCL)-2 as well as IFN-α/β and multiple anti-viralIn reviewproteins (Yu et al., 2014; Ballak et al., 2015), indicating that adipose cells are able to trigger innateantiviral responses. In this Research Topic, Igata et al., performed a global transcriptomic study inporcine intramuscular mature adipocytes following the stimulation with TLR2, TLR3, and TLR4ligands. Interestingly, the work demonstrated that porcine adipocytes, similar to human and mouse cells,are able to respond to TLR3 activation by increasing the expression of several genes (CCL2, CCL8,CCL5, CCL3L1, IL1β, and IL12) that participate in the antiviral inflammatory responses. This workopens the doors for future research on the response of adipocytes in the defense of viral infections in theporcine host, as well as its potential use as a human model.Interestingly, zebrafish has become a well-recognized animal model to study host-microbeimmuneinteractions because of the diverse set of laboratory tools available for these cyprinids,including the possibility of generating germ-free individuals or the in vivo imaging of specific immunecell populations in whole transgenic organisms. Lopez Nadal et al., revised the practical advantages ofzebrafish and discussed how this model sheds light on the mechanisms by which feed influences hostmicrobe-immune interactions and ultimately fish health and resistance to infections. As an interestingexample of the use of the zebrafish model for the study of immunomodulatory feeds Ikeda-Ohtsubo etal., reported the capacity of a fucose-rich sulfated polysaccharide called fucoidan, extracted from edibleseaweed Cladosiphon okamuranus, to modulate microbiota and immune responses.The collection of reviews and original research articles presented under this Research Topicprovide a comprehensive set of information on the potential of nutritional interventions to beneficiallymodulate antiviral immune responses in both humans and animals. The editors hope that this topic willact as a potent stimulus for further research in this growing and exciting area of the NutritionalImmunology.

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