Activation of mucosal immunity and novel prophylactic and therapeutic strategy in combating COVID-19

Coronavirus disease 2019 (COVID-19) emerges as an expeditiously growing pandemic, in the human population caused by the highly transmissible RNA virus severe acute respiratory syndrome of coronavirus 2 (SARS-CoV-2). Prognosis of SARS-CoV-2 infection predominantly occurs at the angiotensin-converting enzyme 2 receptor and transmembrane protease serine type 2 positive (ACE2 + TMPRSS2)+ epithelial cells of the mucosal surface like nasal, oral mucosae, and/or the conjunctival surface of the eye where it has interacted along with the immune system. The primary host response towards the pathogen starts from an immune microenvironment of nasopharynx-associated lymphoid tissue (NALT) and mucosa-associated lymphoid tissue (MALT). The presence of exhausted lymphocytes, lymphopenia, pneumonia and cytokine storm is the hallmark of COVID-19. The multifaceted nature of co-morbidity factors like obesity and type 2 diabetes and its effects on immunity can alter the pathogenesis of SARS-CoV-2 infection. Adipose tissue is a crucial endocrine organ that secretes a plethora of factors like adipokines, cytokines, and chemokines that have a profound impact on metabolism and augments the expression of mucosal pro-inflammatory cytokines, like tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), and the interleukin-12 (IL-12)/IL-23. Mucosal immunization could be a superior approach to activate mucosal and systemic immune responses against pathogenic invasion at mucosal surface entry ports. Mucosal vaccines are also able to generate strong systemic humoral immunity—required to neutralize any virus particle that dodges the primary immune response. To develop an efficient vaccine against mucosal pathogens, considering the designing of the delivery route, immunomodulatory features, and adjuvants are very important. In this article, we further provide evidence to understand the significant role of mucosal immunity, along with secretory and circulating immunoglobulin A (IgA) antibodies in generating a novel mucosal vaccine against COVID-19. Moreover, along with mucosal vaccines, we should look for combination treatment strategies with plant bioactive molecules. Glycan-binding lectins against viral proteins for targeted activation of mucosal immune response are one of such examples. This might play a promising role to halt this emerging virus.

Is Sunflower Cooking Oil Desirable for Colorectal Cancer? In Vivo Studies on Azoxymethane-Induced Colon Cancer in Rats

Background: The incorporation of oils in the diet may have promoting or inhibitory effects on Colorectal Cancer (CRC). In this study, azoxymethane (AOM) was used to mimic CRC in rats and the effect of sunflower oil on cancer progression in the colon of the rats was tested. Objective: This study was conducted to investigate the effect of sunflower oil on preneoplastic cancer properties on the colonic mucosal surface for tumors and the aberrant crypt foci (ACF). Methods: Six weeks old Sprague-Dawley male rats were randomized into 4 groups of 6 rats each, namely naïve, positive control, negative control and sunflower oil-fed. CRC was induced by AOM by subcutaneous injection of 20 mg/kg. After CRC induction, the rats were given respective treatment of either basal diet (naïve group), 10 mg/kg indomethacin (positive control), 0.9% saline (negative control), and 7% sunflower oil (experimental group) daily by oral gavage for 42 days. Rats were sacrificed by cervical dislocation; colon samples were visually observed for any tumors on the colonic mucosal surface and evaluated for ACF; histopathological examinations were also performed. Results: The mean body weights of the rats were similar in all groups as per one-way ANOVA. A total of 3 ACF were found in the negative group while none were observed in others. The crypts appeared regular with circular luminal openings and were arranged closely packed together in the naïve group. Crypts in the positive and treated group had a similar appearance like naïve group. Conclusion: Sunflower oil inhibition of the preneoplastic cancer ACF properties were tested but were found to be insignificant when administered during CRC treatment or management. However long-term experiment with a greater number of days will yield better development of tumor and ACF development and will be useful identifying the molecular mechanism.

Colonizing Microbes, IL-10 and IL-22: Keeping the Peace at the Mucosal Surface

Our world is filled with microbes. Each multicellular organism has developed ways to interact with this microbial environment. Microbes do not always pose a threat; they can contribute to many processes that benefit the host. Upon colonization both host and microbes adapt resulting in dynamic ecosystems in different host niches. Regulatory processes develop within the host to prevent overt inflammation to beneficial microbes, yet keeping the possibility to respond when pathogens attempt to adhere and invade tissues. This review will focus on microbial colonization and the early (innate) host immune response, with special emphasis on the microbiota-modifying roles of IL-10 and IL-22 in the intestine. IL-10 knock out mice show an altered microbial composition, and spontaneously develop enterocolitis over time. IL-22 knock out mice, although not developing enterocolitis spontaneously, also have an altered microbial composition and increase of epithelial-adherent bacteria, mainly caused by a decrease in mucin and anti-microbial peptide production. Recently interesting links have been found between the IL-10 and IL-22 pathways. While IL-22 can function as a regulatory cytokine at the mucosal surface, it also has inflammatory roles depending on the context. For example, lack of IL-22 in the IL-10–/– mice model prevents spontaneous colitis development. Additionally, the reduced microbial diversity observed in IL-10–/– mice was also reversed in IL-10/IL-22 double mutant mice (Gunasekera et al., 2020). Since in early life, host immunity develops in parallel and in interaction with colonizing microbes, there is a need for future studies that focus on the effect of the timing of colonization in relation to the developmental phase of the host. To illustrate this, examples from zebrafish research will be compared with studies performed in mammals. Since zebrafish develop from eggs and are directly exposed to the outside microbial world, timing of the development of host immunity and subsequent control of microbial composition, is different from mammals that develop in utero and only get exposed after birth. Likewise, colonization studies using adult germfree mice might yield different results from those using neonatal germfree mice. Lastly, special emphasis will be given to the need for host genotype and environmental (co-housing) control of experiments.

Elucidating bacterial adhesion to mucosal surface by an original AFM approach

Background Fish skin represents an ancient vertebrate mucosal surface, sharing characteristics with other mucosal surfaces including those of the intestine. The skin mucosa is continuously exposed to microbes in the surrounding water and is therefore important in the first line defense against environmental pathogens by preventing bacteria from accessing the underlying surfaces. Understanding the microbe-host interactions at the fish skin mucosa is highly relevant in order to understand and control infection, commensalism, colonization, persistence, infection, and disease. Here we investigate the interactions between the pathogenic bacteria Aeromonas salmonicida (A. salmonicida) and Yersinia ruckeri (Y. ruckeri), respectively, and the skin mucosal surface of Atlantic salmon fry using AFM force spectroscopy. Results The results obtained revealed that when retracting probes functionalized with bacteria from surfaces coated with immobilized mucins, isolated from salmon mucosal surfaces, rupture events reflecting the disruption of adhesive interactions were observed, with rupture strengths centered around 200 pN. However, when retracting probes functionalized with bacteria from the intact mucosal surface of salmon fish fry no adhesive interactions could be detected. Furthermore, rheological measurements revealed a near fluid-like behavior for the fish fry skin mucus. Taken together, the experimental data indicate that the adhesion between the mucin molecules within the mucous layer may be significantly weaker than the interaction between the bacteria and the mucin molecules. The bacteria, immobilized on the AFM probe, do bind to individual mucins in the mucosal layer, but are released from the near fluid mucus with little resistance upon retraction of the AFM probe, to which they are immobilized. Conclusion The data provided in the current paper reveal that A. salmonicida and Y. ruckeri do bind to the immobilized mucins. However, when retracting the bacteria from intact mucosal surfaces, no adhesive interactions are detected. These observations suggest a mechanism underlying the protective function of the mucosal surface based on the clearing of potential threats by adhering them to loosely attached mucus that is subsequently released from the fish skin.

Effect of Diode Laser on the Candida Albicans Colonization in Complete Denture Wearers

This study aimed to investigate the effect of diode laser on Candida albicans colonization in complete denture patients. A total of 40 complete maxillary dentures wearers were studied in this cross-sectional study. Dentures were then randomly divided into two groups. In the first group, as the control group, no intervention was made. In the second group, the mucosal surface of dentures was exposed to laser irradiation by the diode laser with a wavelength of 940 nm with 100 mW for 30 seconds before delivery. Samples were collected from the mucosal surface of the upper dentures on the determined days. All collected colonies were counted. Clinical outcome was evaluated regarding the colonization of Candida albicans reported by CFU. The difference in colony counts results between the two groups was evaluated by the Mann-Whitney test. Statistical significance was assumed if p<0.05. The results showed that laser irradiation was significantly effective in reducing Candida colonization. The lower density of the colonies was seen in the laser group compared to the control group on the 15th and 60th days after denture delivery (P = 0.002) and (P = 0.003), respectively. Generalization our data into the clinical setting, it can be proposed that a direct laser-based approach can significantly reduce the colonization of Candida albicans. It can also be concluded that laser light at specific wavelengths could be a promising novel strategy for preventing denture stomatitis.

Neglected roles of IgG Fc-binding protein secreted from airway mucin-producing cells in protecting against SARS-CoV-2 infection

Both innate immunity and acquired immunity are involved in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. The induction of Abs that neutralize the virus has been described, and certain Abs against endemic coronaviruses may cross-react with SARS-CoV-2. Detailed mechanisms to protect against the pandemic of SARS-CoV-2 remain unresolved. We previously reported that IgG Fc-binding protein (Fcγbp), a unique, large molecular weight, and mucin-like secretory Fc receptor protein, secreted from goblet cells of human small and large intestine, mediates the transportation of serum IgG onto the mucosal surface. In this review, we show that mucous bronchial gland cells and some goblet cells are immunoreactive for Fcγbp. Fcγbp traps the cross-reactive (both neutralizing and non-neutralizing) IgG bound to the virus and can consequently eliminate the virus from the mucosal surface to decrease viral loads. Fcγbp can also suppress immune overreaction by interfering with Fc-binding by macrophages and competing with complement fixation. Fcγbp secreted from mucin-producing cells of the airway functions as an important anti-infection mucosal defense. The Fcγbp-mediated mechanism can be a key factor in explaining why SARS-CoV-2 is less infective/lethal in children, and may also be involved in the unique Ab response, recurrent infection, and effects of serum therapy and vaccination.

Dieulafoy Lesion as a Source of Bleeding: A Report of Two Clinical Cases

Summary Dieulafoy’s lesion is a rare source of gastrointestinal bleeding. It can be found anywhere in the gastrointestinal tract, but is most commonly seen in the proximal third of the stomach. It is a submucosal artery, adjacent to the mucosal surface, with no evidence of superficial ulcers. Lesions are routinely diagnosed and treated endoscopically. Their frequency is currently not well known, because as Dieulafoy lesions can be easily missed during endoscopy, and bleeding lesions are sometimes misidentified.In this article, we describe two cases of bleeding from the upper gastrointestinal tract, manifested by hematemesis and melena. Bleeding was successfully managed endoscopically by means of injection of adrenaline solution and application of an endoscopic hemoclip.

Electron-Microscopic Studies on the Palatine Tonsil of the Buffalo (Bubalus bubalis)

The study examined the ultrastructural features of the palatine tonsils of the local mixed breed of adult buffaloes using scanning and transmission electron microscopy. The tissue samples collected from the palatine tonsils were fixed in 2% glutaraldehyde solution and processed for scanning and transmission electron microscopy. The scanning electron microscopy of the tonsil's surface epithelium presented folded mucosa consisting of folds divided by shallow grooves. The mucosal surface was having a squamous arrangement of cells that were delineated from the adjacent cells. These cells at higher magnification presented the microplicae, which appeared as if filled with material. A few small duct openings were irregularly placed throughout the mucosal surface. The transmission electron-microscopy elaborated structural details of the distinct strata of the surface and reticular epithelia, the cell organelles as well as the lymphocytes migration across the high endothelial venules. The vesiculo-vacuolar organelle was also observed. The study provided detailed ultramicroscopic features of the palatine tonsil, which might play a significant role in the induction of immunity against ingested antigens sampled at the mucosal surface.