Basal body temperature increases the host’s resistance to influenza virus and SARS-CoV-2 infection

A recent article was published in search field* The prepress server showed that elevated body temperature increases the resistance of the host dependent microbes against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A infection.

Study: Elevated body temperature increases the resistance of the intestinal microbiota-dependent host to influenza A virus and SARS-CoV-2 infection. Image Credit: iunewind / Shutterstock

background

Respiratory diseases, such as influenza and coronavirus disease 2019 (COVID-19), cause significant mortality and morbidity, primarily affecting the elderly. Fever is a common feature of COVID-19 and influenza, although its physiological significance in fighting viral infection among hosts is unclear. The significance of additional age-related alterations in host variants other than type I interferons (IFNs) indicating susceptibility to influenza virus is unknown.

Multiple studies have shown that the composition of the gut microbiota in both animals and humans varies with age. In addition, as people age, the average body temperature decreases. Although it is becoming increasingly clear that the gut microbiota in addition to its metabolites is essential for the prevention of influenza infection, the effects of core body temperature on host defense against influenza virus infection are fundamentally uncertain.

The authors of the current study previously demonstrated that after intranasal treatment with a sub-lethal dose of 30 pfu of influenza virus, mice exposed to a high ambient temperature of 36 °C show impaired virus-selective CD8+ T-cell reactivity and antibody generation. On the other hand, the effect of external temperature on host resistance to a deadly influenza virus challenge is still unknown.

about studying

In this study, scientists studied the effect of basal and external body temperature on a host’s resistance to influenza infection. They tested the host’s resistance to SARS-CoV-2 or influenza virus infection by exposing mice to a high ambient temperature of 36°C.

Mice were housed at 36, 22 or 4 °C for 1 week before infection with influenza virus. Mice exposed to high heat, cold, and room temperature (RT) were intranasally infected with influenza A virus-adapted A/Puerto Rico/8/1934 (PR8) mice and maintained at 36, 22 or 4 °C throughout the evaluations to explore the effect of temperature The body’s primary protection from influenza virus infection.

The authors housed mice at 36, 34, 28, or 22 °C before they were infected with the influenza virus to determine the minimum core body temperature needed to protect against infection. They infected mice treated with antibiotics (Abx) or fed low fiber (LF) exposed to high heat to see if intestinal microbial metabolites or spores are required to improve the host’s resistance to influenza virus infection.

The investigators performed gas chromatography-mass spectrometry (GC-MS), time-of-flight capillary electrophoresis (CE-TOFMS), liquid chromatography-tandem mass spectrometry (LC-MS/MS)-assessment of serum centered metabolites, cyclic contents, And livers of naïve mice maintained at 36, 22, or 4 °C for a week to evaluate the mechanisms underlying a metabolite induced by enterococci led to host resistance in mice exposed to high temperature to influenza infection.

Furthermore, the team examined the inhibitory effect of bile acids on SARS-CoV-2 infection. In the absence or presence of bile acids, they infected VeroE6/TMPRSS2 cells with SARS-CoV-2. Furthermore, the scientists examined the relationship between bile acid titer in the plasma of COVID-19 patients and disease severity.

consequences

The results of the study showed that exposing mice to high ambient temperatures of up to 36°C enhances the host’s resistance against viral pathogens such as influenza and SARS-CoV-2. Rats exposed to elevated temperatures raise their basal body temperature above 38°C, allowing more bile acid to be produced in a manner dependent on the gut microbiota and serum.

Elevated body temperature increases the resistance of the host dependent on intestinal microbes to influenza virus infection.  Mice were kept at 22, 28, 34 or 36 °C for 7 days before infection with influenza virus and throughout the infection.  a, The body temperature of naive mice was measured maintained at 22, 28, 34 or 36 °C.  bd, mice maintained at 22, 28, 34, or 36 °C were infected intranasally with 1000 pfu of influenza virus.  Mortality (b), core body temperature (c) and virus titer in lung lavage (d) were measured on the indicated days after challenge.  e,f, LF-fed, Abx, and control mice that were kept at 36 °C were intranasally infected with 1000 pfu of influenza virus.  Mortality (e) and core body temperatures (f) were measured on the indicated days after the challenge.Elevated body temperature increases the resistance of the host dependent on intestinal microbes to influenza virus infection. Mice were kept at 22, 28, 34 or 36 °C for 7 days before infection with influenza virus and throughout the infection. a, The body temperature of naive mice was measured maintained at 22, 28, 34 or 36 °C. Bahraini dinar Mice kept at 22, 28, 34 or 36 °C were intranasally infected with 1000 pfu of influenza virus. death rate (B), basal body temperatures (c), washes the virus titer in the lung (Dr) on the specified days after the challenge. he is , LF-fed, Abx-treated, and control mice at 36 °C were intranasally infected with 1000 pfu of influenza virus. death rate (e) and basal body temperatures (F) on the specified days after the challenge.

By restricting viral replication and neutrophil-dependent tissue damage, deoxycholic acid (DCA) induced by the gut microbiota as well as plasma membrane-associated Takeda G-protein-coupled receptor 5 (TGR5) increases host resistance to infection with influenza virus.

Moreover, Syrian hamsters were protected from acute SARS-CoV-2 infection by DCA in addition to a nuclear XR receptor (FXR) agonist. In addition, compared to the mild disease group, the plasma of SARS-CoV-2 individuals with moderate disease or two diseases had lower levels of specific bile acids.

Overall, the present findings reveal an unexpected pathway by which resistance to SARS-CoV-2 and influenza virus increased among hosts in a gut microbiome-dependent manner via virus-induced high fever.

Conclusions

Study results described a previously unknown relationship between host viral infection resistance, gut microbial functioning, and core body temperature. Researchers have discovered that exposing mice to a high ambient temperature of 36 degrees Celsius raises body temperature and enhances the host’s resistance to SARS virus or influenza virus infection. Furthermore, the study found that activation of the gut microbiota based on elevated body temperature raises bile acid concentrations in the gut and serum, which reduces viral replication and adverse inflammatory responses after influenza and SARS virus infection.

The present article adds notably to the understanding of how host resistance to SARS-CoV-2 and influenza infection is increased by basal body temperature. The current finding that specific bile acids are reduced in the plasma of individuals with mild 1/2 COVID-19 may explain the diversity in clinical disease manifestations in humans and help mitigating strategies for COVID-19 outcomes.

*Important note

Preprints with search field Publication of primary scientific reports that have not been peer-reviewed and therefore should not be considered conclusive, guide clinical practice/health-related behaviour, or be treated as established information.

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