A study investigating the role of cytokines during SARS-CoV-2 infection in rhesus monkeys

In a recent study posted on Bio Rxiv*Preprint server, US researchers, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in rhesus macaques.

study: IL-10 suppresses T-cell proliferation while promoting tissue-resident memory cell formation during SARS-CoV-2 infection in rhesus monkeysImage credit: StudioMolekuul / Shutterstock

Background

IFNγ is a pro-inflammatory cytokine, whereas IL-10 is an anti-inflammatory cytokine. These two distinct pathways determine the balance between inflammation and SARS-CoV-2 replication during the onset or early stages of coronavirus disease 2019 (COVID-19). However, the importance of these cytokines during SARS-CoV-2 infection has been largely unexplored.

About research

In this study, researchers used a non-human primate (NPH) model to measure changes in pulmonary inflammation, viral replication, and cell-mediated immune responses to SARS-CoV-2 after blocking cytokine pathways. did. The study had a pre-specified endpoint between 28 and 35 days post-infection.

The team created three treatment groups of five male rhesus monkeys, aged 2.5 to 5 years and weighing 3.5 to 5 kilograms. They infected test animals with his SARS-CoV-2 in five waves, each wave infecting one animal per treatment group (three total).

Researchers used HEK-Blue^TMs Reporter cell line for quantification in vitro IL-10 and IFNγ signaling. The color change response indicated the magnitude of cytokine signaling, which the team quantified using a spectrophotometer at 650 nanometers. They used f-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) to image the thorax of infected macaques. They identified a volume of interest (VOI) or lesion in each chest scan obtained on day 2 or 6 and transferred it to registered PET/CT images to determine the lesion volume or FDG. We assessed changes in the uptake of

During necropsy of the animals, the team separately treated lesions that appeared contiguous on PET/CT but resulted from inflammation in multiple lung lobes. In addition, they scanned the upper abdomen, including the spleen and transverse colon, as well as the head and neck.it helped them decide ^(18F)FDG uptake in tonsils and nasal turbinates.

Finally, the researchers harvested the euthanized animal’s lungs and mounted airways, nasal turbinates, salivary glands, tonsils, spleens, tissues, and lymph nodes.In the lung, they assessed parenchymal localization T cellson the other hand, they used lymph node tissue for ribonucleic acid (RNA) isolation, histological analysis, and single-cell preparation for flow cytometry.

Survey results

IFNγ blockade reduced germinal center formation in reactive lymph nodes, but had little or no effect on the characteristics of B or T cell responses. The researchers did not assess the possible effects, if any, of her IFNγ on myeloid cell function. However, they found an interesting effect of IL-10 on SARS-CoV-2-specific T cell responses.

First, IL-10 inhibited the magnitude of virus-specific T cell responses in the circulation, lower respiratory tract, and lung lymph nodes. Analysis of the expression of the proliferation marker Ki-67 gene confirmed that IL-10 did not prolong the cycle of virus-specific T cells and mediated them during the early clonal burst. Second, IL-10 accelerated the rate at which SARS-CoV2-specific T cells differentiated into tissue-resident memory T cells (T_RM) monocytes to increase the production of tumor necrosis factor-beta (TGFβ), which in turn promotes T cells on the mucosal surface of the lower respiratory tract_RM cell phenotype.

Strikingly, rhesus monkeys did not display SARS-CoV-2-specific T cell responses in the nasal mucosa. Indeed, IL-10 blockade reduced the number of T._RM cells of the nasal mucosa. However, studies in mice have detected SARS-CoV-2-specific T._RM cells of the nasal mucosa. Research data pointed out that increased IFNγ may lead to enhanced control of SARS-CoV-2 replication. Similarly, providing exogenous IL-10 during mucosal vaccination may enhance the formation of tissue-resident memory T cells. In other words, research data may have implications for targeting these cytokines as adjuvants for COVID-19 vaccination. The authors cautioned that study results were limited to mild COVID-19 settings and that IFNγ and IL-10 may have different functional roles during severe COVID-19. Future studies using the NHP model of -19 pneumonia may shed light on the cellular and molecular mechanisms of immune-mediated lung injury.

Conclusion

The study results showed that both cytokines, IFNγ and IL-10, do not play critical roles in controlling SARS-CoV-2 replication in the rhesus monkey model. IFNγ blockade reduced lung inflammation to some extent but had no effect on innate lymphocytes. Neutralizing antibody, or antigen-specific T cells. On the other hand, IL-10 blockade transiently increased lung inflammation, suppressed the accumulation of SARS-CoV-2-specific T cells in the lower respiratory tract, and promoted T._RM on respiratory mucosal surfaces.Since these cytokines had virtually no effect viral loadSARS-CoV-2 infection in all test animals eventually resolved.

*Important Notices

Bio Rxiv We publish a non-peer-reviewed, preliminary scientific report and should not be taken as conclusive, to guide clinical practice/health-related actions, or to be treated as established information.