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Complement Proteins, Gut Microbiota and Immune Response: A Complex Interplay

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Mason Walker
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Complement Proteins, Gut Microbiota and Immune Response: A Complex Interplay

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The Intricate Role of Complement Proteins

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Recent research has shed light on the critical role of gut cells in producing complement proteins that are instrumental in protecting against pathogens. Through experiments conducted in mice, scientists discovered that certain gut cells, known as stromal cells, are responsible for producing these crucial proteins, specifically protein C3.

Upon infection with the disease-causing bacterium Citrobacter rodentium, the gut levels of C3 in the mice increased significantly. Furthermore, it was established that C3 aids immune cells in engulfing and eliminating the invading pathogens. Interestingly, mice that were bred to lack C3 showed lower survival rates and experienced weight loss following infection, underlining the indispensable role of complement proteins in the immune response.

Gut Microbiota as a Shield against Respiratory Viruses

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In a fascinating revelation, certain segmented filamentous bacteria (SFB), when naturally present or introduced into the intestinal microbiome, were found to enable the lungs' alveolar macrophages to disable viral infections, thereby protecting against respiratory illnesses. This includes severe diseases like respiratory syncytial virus (RSV) and SARS-CoV-2, the virus that causes COVID-19.

Co-senior author of the study, Andrew T. Gewirtz, suggests that other gut bacteria may play a similar protective role, and research is ongoing to identify them. It is hypothesized that SFB may activate the complement system within the body's greater immune system, marking viruses for phagocytosis. While this research is promising, it's still in its early stages, and it's too soon to make any concrete recommendations.

Microbiota-Gut-Brain Axis and the Influence of Virome

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A study involving mice has found a relationship between stress-induced behavior changes and the gut virome. Chronic stress resulted in behavioral, immune, and bacteriome alterations in mice associated with changes in the bacteriophage class Caudoviricetes and unassigned viral taxa. A transfer of the fecal virome helped protect against stress-related behavior consequences and restored stress-induced changes in select circulating immune cell populations, cytokine release, bacteriome alterations, and gene expression in the amygdala. This underlines the potential role of the virome in modulating the microbiota-gut-brain axis during stress.

The Role of Plasmid Encoded Toxin Pet in Immune Evasion

Evasion of the immune system by harmful bacteria is a significant challenge. Research on the role of the plasmid encoded toxin Pet, an autotransporter protein of the serine protease autotransporters of Enterobacteriaceae (SPATE) family, demonstrates its ability to inhibit the complement system proteins. The proteolytic activity of Pet can interfere with the alternative and terminal pathways of the complement system, leading to innate immune evasion.

Link between Gut Microbiota Composition and Respiratory Virus Infections

A compelling study found that the composition of the gut microbiota influences susceptibility to respiratory virus infections and their severity. The presence of segmented filamentous bacteria altered basally resident alveolar macrophages to resist influenza virus infection depletion and inflammatory signaling. This suggests that gut microbiota composition not only influences susceptibility to respiratory virus infection but could also determine long-term health post-infection.

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