Publication Date:
2013-08-24
Description:
Nociceptor sensory neurons are specialized to detect potentially damaging stimuli, protecting the organism by initiating the sensation of pain and eliciting defensive behaviours. Bacterial infections produce pain by unknown molecular mechanisms, although they are presumed to be secondary to immune activation. Here we demonstrate that bacteria directly activate nociceptors, and that the immune response mediated through TLR2, MyD88, T cells, B cells, and neutrophils and monocytes is not necessary for Staphylococcus aureus-induced pain in mice. Mechanical and thermal hyperalgesia in mice is correlated with live bacterial load rather than tissue swelling or immune activation. Bacteria induce calcium flux and action potentials in nociceptor neurons, in part via bacterial N-formylated peptides and the pore-forming toxin alpha-haemolysin, through distinct mechanisms. Specific ablation of Nav1.8-lineage neurons, which include nociceptors, abrogated pain during bacterial infection, but concurrently increased local immune infiltration and lymphadenopathy of the draining lymph node. Thus, bacterial pathogens produce pain by directly activating sensory neurons that modulate inflammation, an unsuspected role for the nervous system in host-pathogen interactions.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3773968/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3773968/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chiu, Isaac M -- Heesters, Balthasar A -- Ghasemlou, Nader -- Von Hehn, Christian A -- Zhao, Fan -- Tran, Johnathan -- Wainger, Brian -- Strominger, Amanda -- Muralidharan, Sriya -- Horswill, Alexander R -- Bubeck Wardenburg, Juliane -- Hwang, Sun Wook -- Carroll, Michael C -- Woolf, Clifford J -- 5F32NS076297/NS/NINDS NIH HHS/ -- 5P01NS072040/NS/NINDS NIH HHS/ -- 5R01AI039246/AI/NIAID NIH HHS/ -- P01 NS072040/NS/NINDS NIH HHS/ -- P01AI078897/AI/NIAID NIH HHS/ -- P30 HD018655/HD/NICHD NIH HHS/ -- P30-HD018655/HD/NICHD NIH HHS/ -- R01 AI039246/AI/NIAID NIH HHS/ -- R01 NS039518/NS/NINDS NIH HHS/ -- R37 NS039518/NS/NINDS NIH HHS/ -- R37NS039518/NS/NINDS NIH HHS/ -- England -- Nature. 2013 Sep 5;501(7465):52-7. doi: 10.1038/nature12479. Epub 2013 Aug 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23965627" target="_blank"〉PubMed〈/a〉
Keywords:
Action Potentials
;
Animals
;
Bacterial Load
;
Calcium Signaling
;
Female
;
Hemolysin Proteins/metabolism
;
Host-Pathogen Interactions
;
Hot Temperature
;
Hyperalgesia/microbiology
;
Immunity, Innate
;
Inflammation/immunology/metabolism/*microbiology/pathology
;
Lymphatic Diseases/immunology/microbiology/pathology
;
Male
;
Mice
;
Mice, Inbred C57BL
;
Monocytes
;
Myeloid Differentiation Factor 88/immunology
;
N-Formylmethionine Leucyl-Phenylalanine/metabolism
;
NAV1.8 Voltage-Gated Sodium Channel/deficiency/immunology/metabolism
;
Neutrophils
;
Nociceptors/*metabolism
;
Pain/immunology/metabolism/*microbiology/*physiopathology
;
Protein Stability
;
Staphylococcal Infections/immunology/metabolism/microbiology
;
Staphylococcus aureus/immunology/metabolism/*pathogenicity
;
Toll-Like Receptor 2/immunology
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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