title: Quiescent innate response to infective filariae by human Langerhans cells suggests a strategy of immune evasion.
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 vitro and 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 of the proinflammatory cytokines IL-1β, gamma interferon (IFN-γ), IL-6, or IL-10. Interestingly, cocultures of KC and LC produced significantly more IL-18, IL-1α, and IL-8 than did cultures of LC alone, although exposure of the cocultures to live L3 did not result in altered cytokine production. Microarray examination of ex vivo LC from skin blisters that were 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.
authors: Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors: Alexis
authors: A
authors: Boyd
authors: Sasisekhar
authors: S
authors: Bennuru
authors: Yuanyuan
authors: Y
authors: Wang
authors: Vivornpun
authors: V
authors: Sanprasert
authors: Melissa
authors: M
authors: Law
authors: Damien
authors: D
authors: Chaussabel
authors: Thomas B
authors: TB
authors: Nutman
authors: Roshanak Tolouei
authors: RT
authors: Semnani
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000032:analysis / Q000276:immunology; D017178:Brugia malayi / Q000276:immunology*; D015820:Cadherins / Q000378:metabolism; D020170:Caspase 1 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D057131:Immune Evasion / Q000276:immunology*; D007113:Immunity, Innate; D007801:Langerhans Cells / Q000276:immunology* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012867:Skin / Q000276:immunology / Q000469:parasitology
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D016207:Cytokines; D006684:HLA-DR Antigens; D012333:RNA, Messenger; D020170:Caspase 1