Quiescent Innate Response to Infective Filariae by Human Langerhans Cells Suggests aStrategy of Immune Evasion

Academic Article

Abstract

  • Filarial infection is initiated by mosquito-derived third-stage larvae (L3) deposited on the skin that transit through the epidermis, which contains Langerhans cells (LC) and keratinocytes (KC), among other cells. This earliest interaction between L3 and the LC likely conditions the priming of the immune system to the parasite. To determine the nature of this interaction, human LC (langerin+ E-cadherin+ CD1a+) were generated in vitroand exposed to live L3. LC exposed to live L3 for 48 h showed no alterations in the cell surface markers CD14, CD86, CD83, CD207, E-cadherin, CD80, CD40, and HLA-DR or in mRNA expression of inflammation-associated genes, such as those for interleukin 18 (IL-18), IL-18BP, and caspase 1. In contrast to L3, live tachyzoites of Toxoplasma gondii, an intracellular parasite, induced production of CXCL9, IP-10, and IL-6 in LC. Furthermore, preexposure of LC to L3 did not alter Toll-like receptor 3 (TLR3)- or TLR4-mediated expression ofthe proinflammatory cytokines IL-1β, gamma interferon (IFN-α), IL-6, or IL-10. Interestingly, cocultures of KC and LC produced significantly more IL-18, IL-1γ, and IL-8 than did cultures of LC alone, although exposure of the cocultures to live L3 did not result inaltered cytokine production. Microarray examination of ex vivo LC from skin blisters thatwere exposed to live L3 also showed few significant changes in gene expression compared with unexposed blisters, further underscoring the relatively muted response of LC to L3. Our data suggest that failure by LC to initiate an inflammatory response to the invasive stage of filarial parasites may be a strategy for immune evasion by the filarial parasite. © 2013, American Society for Microbiology.
  • Authors

    Published In

    Digital Object Identifier (doi)

    Pubmed Id

  • 19693516
  • Author List

  • Boyd A; Bennuru S; Wang Y; Sanprasert V; Law M; Chaussabel D; Nutman TB; Semnani RT
  • Start Page

  • 1420
  • End Page

  • 1429
  • Volume

  • 81
  • Issue

  • 5