Reduced toll-like receptor 4 and substance P gene expression is associated with airway bacterial colonization in children.
Neuro-immune interactions are increasingly relevant to human health and disease. The neuropeptide Substance P also has antibacterial activity and bears similarities to the innate immune antibacterial defensins. This suggests possible co-regulation of neuropeptide and innate immune mediators. In this study, non-bronchoscopic bronchoalveolar lavage (BAL) was performed on 69 children. BAL was examined for cellular profile, microbiology (bacteria, virus) and gene expression for TLRs 2, 3, 4; chemokine receptors (CCR3, CCR5, CXCR1); neurotrophins and neurokinin genes (TAC1, TAC3, CGRP, NGF). In children with bacterial colonization (n=10) there was an airway inflammatory response with increased BAL neutrophils, IL-8 protein, and CXCR1 expression. Substance P (TAC1) and TLR4 RNA expression were reduced in children with bacterial colonization. TLR3 mRNA was increased in 7.2% (n=5) children with rhinovirus, and there was a non-significant trend to increased TLR2. There is evidence for co-regulation of neurokinin (TAC1) and TLR4 gene expression in airway cells from children with airway bacterial colonization and their reduced expression may be associated with an impaired bacterial clearance.
Grissell
Terry V
TV
Hunter Medical Research Institute, University of Newcastle, John Hunter Hospital, New Lambton, Australia.
Chang
Anne B
AB
Gibson
Peter G
PG
D000293:Adolescent; D018893:Bronchoalveolar Lavage; D001992:Bronchoalveolar Lavage Fluid / Q000382:microbiology*; D002648:Child; D002675:Child, Preschool; D020869:Gene Expression Profiling; D006801:Humans; D007223:Infant; D016209:Interleukin-8 / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D023062:Receptors, Interleukin-8A / Q000378:metabolism; D013373:Substance P / Q000235:genetics*; D015320:Tachykinins / Q000235:genetics / Q000378:metabolism; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism*
D016209:Interleukin-8; D011498:Protein Precursors; D012333:RNA, Messenger; D023062:Receptors, Interleukin-8A; D015320:Tachykinins; D051193:Toll-Like Receptors; C044206:preprotachykinin; D013373:Substance P; D020780:Matrix Metalloproteinase 9