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Interactions of Probiotics with the Immune Cells of Patients with COVID-19 Pneumonia
Ioannis Mitrou1, George Dimopoulos2, Konstantina Dakou3
1Fourth Department of Internal Medicine, National and Kapodistrian University of Athens Medical School, Athens, Greece.
Introduction:
In severe COVID-19, excessive cytokine release may be driven by SARS-CoV-2. We investigated the modulatory effect of probiotics taking into consideration direct interaction with the immune gut cells.
Methods:
Fifty-five patients with confirmed COVID-19 infection were classified by the presence of acute respiratory distress syndrome (ARDS) or not. Peripheral blood mononuclear cells (PBMCs) were isolated and stimulated with lipopolysaccharide (LPS), a preparation of four probiotics (LactoLevure® containing Saccharomyces boulardii, Bifidobacterium lactis BB-12, Lactobacillus acidophilus LA-5, and L. plantarum) and/or recombinant human interferon-gamma (rhIFNγ) and tocilizumab. Cytokine concentrations were measured in cell supernatants. Gene expression of Toll-like receptors 2 (TLR2) and 4 (TLR4) was performed by quantitative real-time polymerase chain reaction (RT-PCR). Results were associated with the level of viremia.
Results:
Probiotics decreased tumor necrosis factor-alpha (TNFα) production by the PBMCs of both ARDS and non-ARDS patients. LPS stimulated the production of interleukin (IL)-1β, IL-6 in non-ARDS patients. IL-6 production was maintained in the presence of probiotics. rhIFNγ enhanced LPS-stimulated cytokine production by PBMCs; this was not the case when PBMCs were stimulated by probiotics. Probiotics upregulated TLR2 and LPS downregulated TLR4 in the PBMCs of patients with ARDS. PBMCs from patients with viremia had more cytokine production by probiotic stimulation.
Conclusion:
Probiotics interact with the immune system of COVID-19 patients by modulating the production of TNFα, IL-1β, and IL-6 in an IFNγ-independent mechanism.
Insights
Probiotics modulate immune responses in COVID-19 patients by reducing pro-inflammatory cytokines like TNFα, IL-1β, and IL-6. This immune modulation occurs independently of interferon-gamma, suggesting a potential therapeutic role for probiotics in managing severe COVID-19.
Area of Science:
- Immunology
- Microbiology
- Virology
Background:
- Severe COVID-19 is associated with excessive cytokine release, potentially driven by SARS-CoV-2.
- The role of gut microbiota, specifically probiotics, in modulating immune responses during COVID-19 requires further investigation.
Purpose of the Study:
- To investigate the modulatory effects of probiotics on immune cells from COVID-19 patients.
- To explore the direct interaction of probiotics with immune gut cells and their impact on cytokine production.
Main Methods:
- Peripheral blood mononuclear cells (PBMCs) from 55 COVID-19 patients (with and without ARDS) were stimulated with probiotics, LPS, and/or rhIFNγ.
- Cytokine concentrations (TNFα, IL-1β, IL-6) and gene expression of TLR2 and TLR4 were measured.
- Results were correlated with viremia levels.
Main Results:
- Probiotics reduced TNFα production in PBMCs from both ARDS and non-ARDS patients.
- Probiotics maintained IL-6 production stimulated by LPS in non-ARDS patients.
- Probiotics upregulated TLR2 and downregulated TLR4 in ARDS patients' PBMCs, with increased cytokine production observed in patients with viremia.
Conclusions:
- Probiotics modulate the immune system in COVID-19 patients by affecting TNFα, IL-1β, and IL-6 production.
- The observed immunomodulation by probiotics occurs through an interferon-gamma-independent mechanism.
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