02663nas a2200349   4500000000100000008004100001260001200042653002500054653003300079653001500112653002200127653003100149653002700180653003300207100001200240700001200252700001500264700001500279700001300294700001500307700001400322700001100336700001200347700002100359700001600380245011500396856008100511300001100592490000700603520168900610022001402299       2021                            d  c01/202110aMycobacterium leprae10aToll-like receptor 9 (TLR-9)10achemokines10aextracellular DNA10ahistone-like protein (Hlp)10ainnate immune response10arespiratory epithelial cells1 aDias AA1 aSilva C1 ada Silva C1 aLinhares N1 aSantos J1 aVivarini A1 aMarques M1 aRosa P1 aLopes U1 aBerrêdo-Pinho M1 aPessolani M00aTLR-9 Plays a Role in Mycobacterium leprae-Induced Innate Immune Activation of A549 Alveolar Epithelial Cells.  uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8397448/pdf/fimmu-12-657449.pdf  a6574490 v123 a<p>The respiratory tract is considered the main port of entry of , the causative agent of leprosy. However, the great majority of individuals exposed to the leprosy bacillus will never manifest the disease due to their capacity to develop protective immunity. Besides acting as a physical barrier, airway epithelium cells are recognized as key players by initiating a local innate immune response that orchestrates subsequent adaptive immunity to control airborne infections. However, to date, studies exploring the interaction of  with the respiratory epithelium have been scarce. In this work, the capacity of  to immune activate human alveolar epithelial cells was investigated, demonstrating that -infected A549 cells secrete significantly increased IL-8 that is dependent on NF-κB activation.  was also able to induce IL-8 production in human primary nasal epithelial cells. -treated A549 cells also showed higher expression levels of human β-defensin-2 (hβD-2), MCP-1, MHC-II and the co-stimulatory molecule CD80. Furthermore, the TLR-9 antagonist inhibited both the secretion of IL-8 and NF-κB activation in response to , indicating that bacterial DNA sensing by this Toll-like receptor constitutes an important innate immune pathway activated by the pathogen. Finally, evidence is presented suggesting that extracellular DNA molecules anchored to Hlp, a histone-like protein present on the  surface, constitute major TLR-9 ligands triggering this pathway. The ability of  to immune activate respiratory epithelial cells herein demonstrated may represent a very early event during infection that could possibly be essential to the generation of a protective response.</p>  a1664-3224