Lactobacillus rhamnosus Restores Antiviral Signaling and Attenuates Cytokines Secretion from Human Bronchial Epithelial Cells Exposed to Cigarette Smoke and Infected with SARS-CoV-2

Abstract

Individuals with chronic obstructive pulmonary disease (COPD) are more susceptible to exacerbation crisis triggered by secondary lung infections due to the dysfunction of antiviral signaling, principally via suppression of IFN-γ. Although the probiotic is known for controlling pulmonary inflammation in COPD, the influence of the Lactobacillus rhamnosus (Lr) on antiviral signaling in bronchial epithelium exposed to cigarette smoke extract (CSE) and viruses, remains unknown. Thus, the present study investigated the Lr effect on the antiviral signaling and the secretion of inflammatory mediators from bronchial epithelial cells (16HBE cells) exposed to CSE and SARS-CoV-2. The 16HBE cells were cultured, treated with Lr, stimulated with CSE, and infected with SARS-CoV-2. The cellular viability was evaluated using the MTT assay and cytotoxicity measured by lactate dehydrogenase (LDH) activity. The viral load, TLR2, TLR3, TLR4, TLR7, TLR8, MAVS, MyD88, and TRIF were quantified using specific PCR. The pro-inflammatory mediators were measured by a multiplex biometric immunoassay, and angiotensin converting enzyme 2 (ACE2) activity, NF-κB, RIG-I, MAD5, and IRF3 were measured using specific ELISA kits. Lr decreased viral load, ACE2, pro-inflammatory mediators, TLR2, TLR4, NF-κB, TLR3, TLR7, and TLR8 as well as TRIF and MyD88 expression in CSE and SARS-CoV-2 -exposed 16HBE cells. Otherwise, RIG-I, MAD5, IRF3, IFN-γ, and the MAVS expression were restored in 16HBE cells exposed to CSE and SARS-CoV-2 and treated with Lr. Lr induces antiviral signaling associated to IFN-γ secreting viral sensors and attenuates cytokine storm associated to NF-κB in bronchial epithelial cells, supporting its emerging role in prevention of COPD exacerbation.

Bifidobacterium longum and Chlorella sorokiniana Improve the IFN Type I-Mediated Antiviral Response in Rotavirus-Infected Cells

“…Nevertheless, some viruses express proteins associated with cellular immunity evasion by inhibiting the antiviral type I interferon pathway [ 7 , 22 , 23 ]. Some probiotics such as Lactobacillus mucosae and Bifidobacterium breve have been shown to restore antiviral signaling by upregulating interferon levels [ 7 , 28 ].…”

Oligosaccharides as Potential Regulators of Gut Microbiota and Intestinal Health in Post-COVID-19 Management

“…The immune system, critical in both the gut and lungs, is believed to mediate the gut–lung axis, along with ACE2 expression in both organs [ 131 ]. Studies reveal that the gut microbiota modulates ACE2 expression in the respiratory system, and that treatment with Lactobacillus rhamnosus can increase ACE2 expression in the lungs, mitigate influenza virus-induced lung injury, and improve lung function [ 132 ]. Various oligosaccharides, including fructo-oligosaccharides, xylooligosaccharides, galacto-oligosaccharides, and pectin-oligosaccharides, have been shown to selectively promote the growth of beneficial gut bacteria such as Bifidobacteria and Lactobacilli .…”

“…The immune system, critical in both the gut and lungs, is believed to mediate the gut-lung axis, along with ACE2 expression in both organs [131]. Studies reveal that the gut microbiota modulates ACE2 expression in the respiratory system, and that treatment with Lactobacillus rhamnosus can increase ACE2 expression in the lungs, mitigate influenza virus-induced lung injury, and improve lung function [132].…”

Bifidobacterium longum and Chlorella sorokiniana Combination Modulates IFN-γ, IL-10, and SOCS3 in Rotavirus-Infected Cells

“…On the other hand, Lactobacillus and Bifidobacterium are associated with restored antiviral signaling by up-regulating interferon levels [30][31][32]. Furthermore, microalgae Chlorella have demonstrated a beneficial immunomodulatory effect against enteric pathogens [6][7][8].…”