Immunomodulatory Role of Microelements in COVID-19 Outcome: a Relationship with Nutritional Status.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19). SARS-CoV-2 infection can activate innate and adaptive immune responses and result in massive inflammatory responses in the disease. A comprehensive understanding of the participation of micronutrients in the immune response to COVID-19 will allow the creation of prevention and supplementation scenarios in malnutrition states. Microelement deficiency can be decisive in the progression of diseases and their optimal levels can act as protective factors, helping to maintain homeostasis. Vitamin A, B, D, selenium, zinc, and copper, through their complementary and synergistic effects, allow the components of innate and adaptive immunity to counteract infections like those occurring in the respiratory tract.Thus, alterations in nutritional status are related to metabolic diseases, systemic inflammation, and deterioration of the immune system that alter the response against viral infections, such as COVID-19. The aim of this review is to describe the micronutrients that play an important role as immunomodulators and its relationship between malnutrition and the development of respiratory infections with an emphasis on severe and critical COVID-19. We conclude that although an unbalanced diet is not the only risk factor that predisposes to COVID-19, a correct and balanced diet, which provides the optimal amount of micronutrients and favors an adequate nutritional status, could confer beneficial effects for prevention and improvement of clinical results. The potential usefulness of micronutrient supplementation in special cases is highlighted.

Immunomodulation by Bifidobacterium animalis subsp. lactis Bb12: Integrative Analysis of miRNA Expression and TLR2 Pathway-Related Target Proteins in Swine Monocytes.

Bifidobacterium animalis subsp. lactis Bb12 is a widely used probiotic that provides numerous health benefits to its host, many due to its immunomodulatory properties. Although the precise mechanism of modulation is still under investigation, several reports associate the interaction of TLR2 with components of the bacterial cell wall inducing a signaling cascade that culminates with the production of cytokines and co-stimulatory molecules. MicroRNAs (miRNAs) have emerged as important post-transcriptional regulators of immune responses, including those toward probiotics. In this study, we analyzed the miRNA expression profile in swine monocytes exposed to Bb12 by using an anti-TLR2 blocking strategy and Bb12 involvement in the regulation of the TLR2 pathway. As a result, the expression of 40 miRNAs was influenced by the treatments (p < 0.01), and 15 differentially expressed miRNAs with validated miRNA-mRNA interactions with around 26 proteins related to the TLR2 pathway were identified. The miRNAs upregulated in response to Bb12 included miR-15a-5p, miR-16-5p, miR-26a-5p, miR-29b-3p, and miR-30d-5p, and the following showed downregulation: miR-181a-5p, miR-19b-3p, miR-21-5p, miR-23a-5p, and miR-221-3p. The expression of let-7c-5p, let-7f-5p, miR-146b-5p, miR-150-5p, and miR-155-5p was increased by Bb12 only when TLR2 was blocked. The identified miRNA common targets were downstream proteins from bacterial recognition via TLR2, such as MyD88, TRAF6, and MAPK members; transcription factors such as NF-κB and AP-1; and cytokines such as IL-6, IL-10, and TNF-α. TLR2 participation was abrogated by anti-TLR2 antibody and suggests that bacterial recognition is complemented by other receptors since there were still changes in the microtranscriptome.

Is periodontal disease a risk factor for severe COVID-19 illness?

Periodontal disease (PD) comprises a group of diseases involving inflammatory aspects of the host and dysbiotic events that affect periodontal tissues and could have systemic implications. Diverse factors and comorbidities have been closely associated with PD such as diabetes, obesity, aging, hypertension, and so on; although, underlying mechanisms or causal associations have not been established completely. Interestingly, these same factors have been widely associated with progression or severe coronavirus disease 2019 (COVID-19), an illness caused by coronavirus SARS-CoV-2. Since inflammatory and dysbiotic factors as well as comorbidities affect systemic health, it is possible that periodontal status indicates the risk of complication of COVID-19. However, assessment of oral health history including periodontal status in COVID-19 patients has not been reported. Knowing PD is associated with severe COVID-19 could help identify risk groups and establish pertinent recommendations.

Cancer-Associated Myeloid Regulatory Cells.

Myeloid cells are critically involved in the pathophysiology of cancers. In the tumor microenvironment (TME), they comprise tumor-associated macrophages (TAMs), neutrophils (TANs), dendritic cells, and myeloid-derived suppressor cells, which are further subdivided into a monocytic subset and a granulocytic subset. Some of these myeloid cells, in particular TAMs and TANs, are divided into type 1 or type 2 cells, according to the paradigm of T helper type 1 or type 2 cells. Type 1-activated cells are generally characterized as cells that aid tumor rejection, while all other myeloid cells are shown to favor tumor progression. Moreover, these cells are often at the basis of resistance to various therapies. Much research has been devoted to study the biology of myeloid cells. This endeavor has proven to be challenging, as the markers used to categorize myeloid cells in the TME are not restricted to particular subsets. Also from a functional and metabolic point of view, myeloid cells share many features. Finally, myeloid cells are endowed with a certain level of plasticity, which further complicates studying them outside their environment. In this article, we challenge the exclusive use of cell markers to unambiguously identify myeloid cell subsets in the TME. We further propose to divide myeloid cells into myeloid regulatory or stimulatory cells according to their pro- or antitumor function, because we contend that for therapeutic purposes it is not targeting the cell subsets but rather targeting their protumor traits; hence, myeloid regulatory cells will push antitumor immunotherapy to the next level.

MicroRNAs: Regulators of TLR2-Mediated Probiotic Immune Responses.

MicroRNAs (miRNAs) are similar in importance to transcription factors and critical to confer accuracy and robustness in gene expression programs and consequently, have emerged as controllers of the immune response. On the other hand, probiotic influence over immune responses against a wide spectrum of health conditions are widely studied but the mechanism for this modulation has not yet completely elucidated. One proposed mechanism involves the receptor-mediated interaction of dendritic cells with components of the cellular membrane and/or secreted peptides of probiotics ending with the production of cytokines. However, the cytokine response elicited by dendritic cells is largely strain-dependent, and not to the same extent. The signaling pathway involved must be tightly regulated in order to be precise and effective; proteins as TNF receptor-associated factor 6 (TRAF6), Interleukin-1 receptor-associated kinase 4 (IRAK4) and Interleukin-1 receptor-associated kinase 3 (IRAK3 or IRAKM) participate in an important way in the nuclear factor kappa B (NF-κB) signaling pathway, which is the main cascade activated in response to probiotics. These proteins can be regulated by miRNAs and alter the immune outcome. This review discusses the current understanding on the participation of miRNAs modulating the TLR2/NF-κB pathway in the innate immune response mediated by probiotics.