Gut microbes extend reach to systemic innate immunity
Nature Medicine 16, 160 (2010).
Authors: Dana J Philpott & Stephen E Girardin
Microbes in the gut can influence distant events, affecting the function of neutrophils in the circulation of mice (pages 228-231). The findings should lead to new studies examining how intestinal microbes affect immunity.
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Recognition of peptidoglycan from the microbiota by Nod1 enhances systemic innate immunity
Nature Medicine 16, 228 - 231 (2010)
Authors: Thomas B Clarke, Kimberly M Davis, Elena S Lysenko, Alice Y Zhou, Yimin Yu & Jeffrey N Weiser
Humans are colonized by a large and diverse bacterial flora (the microbiota) essential for the development of the gut immune system.
A broader role for the microbiota as a major modulator of systemic immunity has been proposed; however, evidence and a mechanism for this role have remained elusive.
We show that the microbiota are a source of peptidoglycan that systemically primes the innate immune system, enhancing killing by bone marrow–derived neutrophils of two major pathogens: Streptococcus pneumoniae and Staphylococcus aureus.
This requires signaling via the pattern recognition receptor nucleotide-binding, oligomerization domain–containing protein-1 (Nod1, which recognizes meso-diaminopimelic acid (mesoDAP)-containing peptidoglycan found predominantly in Gram-negative bacteria), but not Nod2 (which detects peptidoglycan found in Gram-positive and Gram-negative bacteria) or Toll-like receptor 4 (Tlr4, which recognizes lipopolysaccharide).
We show translocation of peptidoglycan from the gut to neutrophils in the bone marrow and show that peptidoglycan concentrations in sera correlate with neutrophil function.
In vivo administration of Nod1 ligands is sufficient to restore neutrophil function after microbiota depletion.
Nod1−/− mice are more susceptible than wild-type mice to early pneumococcal sepsis, demonstrating a role for Nod1 in priming innate defenses facilitating a rapid response to infection.
These data establish a mechanism for systemic immunomodulation by the microbiota and highlight potential adverse consequences of microbiota disruption by broad-spectrum antibiotics on innate immune defense to infection.
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The human body is a symbiotic organism. There are about 10 times more bacteria than human cells in the human body. The average adult has about 4.5 pounds of bacteria in the gastrointestinal system. Ninety percent of our immune system cells are in the gastrointestinal system.
Previously, it was thought that the gastrointestinal bacteria form a passive means of protection from infection. However, this article demonstrates active signaling between the gastrointestinal bacteria and the immune system.
Gastrointestinal bacteria produce peptoglycan, a signal that travels through blood and sera to activate neutrophils as far away as in the bone marrow to become more potent in killing two pathogenic bacteria: Streptococcus pnumoniae and Staphylococcus aureus.
Excessively killing off gut microbia via antibiotic use increases susceptibility to infection by disrupting not only passive interaction but active interaction between the gut microbia and the immune system. The increased occurrence of infection along the gastrointestinal system is sensed by the vagal nerve, which then stimulates sympathetic nervous system activity, increasing perceived stress via norepinephrine signaling.
It is important to assess gastrointestinal problems in psychiatric patients since the presence of these problems may be one of the pathophysiologies underlying various mental illnesses including the the mood disorders (including anxiety disorders).
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