How commensal bacteria modulate immune responses

As you all probably know by now, I grew up in Europe. One of the first things I noticed when dealing with the health system here in the U.S. is -- no, not insurance. Antibiotics! Yes, I'm old school and believe that antibiotics are over-prescribed in this country. You may find it convenient to carry antibiotic creams in your hiking bag and use it over the tiniest scrapes, or that your house cleaner kills 99.99% of germs, but in the end we may pay a price for that. The paper I'm discussing today used antibiotics to manipulate the commensal bacteria population in mice and observed "impaired host protective immunity after either systemic (lymphocytic choriomeningitis virus) or mucosal (influenza virus) infection [1]."

Commensal microbiota consist of tiny organisms such as bacteria, protozoa, fungi, and viruses that live in our skin, upper respiratory and gastrointestinal tracts. The communities in the intestine in particular are extremely beneficial as they guard from competing pathogens and aid our metabolism. In [1] Abt et al. list a number of studies that, all together, seem to indicate that manipulating the commensal bacteria communities results in increased susceptibility to infections and inflammation in certain animal models.

"Consistent with proinflammatory properties, signals from commensal bacteria can act as an adjuvant, augmenting immune responses after intestinal parasitic or bacterial infections. Conversely, commensal bacteria can increase viral infectivity in the gastrointestinal microenvironment. Thus, commensal-derived signals are capable of limiting or exacerbating infection in the intestinal microenvironment."

Clearly, there's a strict interaction between commensal bacteria and the immune system, as the former seems to calibrate the responses of the latter, though it's unclear what mechanisms regulate it. Is it an on-going modulation or is it triggered only in case of an infection? And how does it tune responsiveness to viral pathogens?

"Whether depletion of commensal bacteria selectively regulates inflammasome-dependent pathways or represents broader immunological crosstalk between commensal bacteria and antiviral pathways remains to be determined."

For the experiment, a group of mice were administrated antibiotics orally. They were then either inoculated intravenously with lymphocytic choriomeningitis virus or intranasally with recombinant influenza viruses. The researchers noticed impaired responses in the antibiotic treated mice and a reduced capacity to control viral replication. Once the responsiveness to interferons was restored (interferons are proteins released by cells in order to flag the presence of pathogens), protective antiviral immunity was re-established, indicating that the commensal bacteria had a role in initiating antiviral responses. In particular, they seem to calibrate the activation threshold of innate immune responses.

"Taken together, these data indicate that commensal bacteria provide tonic signals that calibrate the activation threshold and sensitivity of the innate antiviral immune system."

They also point at the use of probiotic treatments as a new strategy against viral infections.

Note that the paper addresses the question of how commensal bacteria modulate host immunity, which is a really interesting find. The warning on the use of antibiotics or any other agent that can harm our exposure to commensal bacteria is an extra thought that I tossed in. Antibiotics have significantly lengthened our life span. But I also believe in the old school "use with moderation" motto. Benefits are easy to spot, but the damage often takes way longer to build.

[1] Michael C. Abt, Lisa C. Osborne, Laurel A. Monticelli, Travis A. Doering, Theresa Alenghat, Gregory F. Sonnenberg, Michael A. Paley, Marcelo Antenus, Katie L. Williams, Jan Erikson, E. John Wherrysend, David Artissend (2012). Commensal Bacteria Calibrate the Activation Threshold of Innate Antiviral Immunity Immunity