PMID- 23050849 OWN - NLM STAT- MEDLINE DCOM- 20130304 LR - 20211021 IS - 1756-3305 (Electronic) IS - 1756-3305 (Linking) VI - 5 DP - 2012 Oct 10 TI - Ixodes scapularis saliva mitigates inflammatory cytokine secretion during Anaplasma phagocytophilum stimulation of immune cells. PG - 229 LID - 10.1186/1756-3305-5-229 [doi] AB - BACKGROUND: Ixodes scapularis saliva enables the transmission of infectious agents to the mammalian host due to its immunomodulatory, anesthetic and anti-coagulant properties. However, how I. scapularis saliva influences host cytokine secretion in the presence of the obligate intracellular rickettsial pathogen Anaplasma phagocytophilum remains elusive. METHODS: Bone marrow derived macrophages (BMDMs) were stimulated with pathogen associated molecular patterns (PAMPs) and A. phagocytophilum. Cytokine secretion was measured in the presence and absence of I. scapularis saliva. Human peripheral blood mononuclear cells (PBMCs) were also stimulated with Tumor Necrosis Factor (TNF)-alpha in the presence and absence of I. scapularis saliva and interleukin (IL)-8 was measured. RESULTS: I. scapularis saliva inhibits inflammatory cytokine secretion by macrophages during stimulation of Toll-like (TLR) and Nod-like receptor (NLR) signaling pathways. The effect of I. scapularis saliva on immune cells is not restricted to murine macrophages because decreasing levels of interleukin (IL)-8 were observed after TNF-alpha stimulation of human peripheral blood mononuclear cells. I. scapularis saliva also mitigates pro-inflammatory cytokine response by murine macrophages during challenge with A. phagocytophilum. CONCLUSIONS: These findings suggest that I. scapularis may inhibit inflammatory cytokine secretion during rickettsial transmission at the vector-host interface. FAU - Chen, Gang AU - Chen G AD - Center for Disease Vector Research and Department of Entomology, University of California-Riverside, Riverside, CA 92521, USA. FAU - Severo, Maiara S AU - Severo MS FAU - Sohail, Mohammad AU - Sohail M FAU - Sakhon, Olivia S AU - Sakhon OS FAU - Wikel, Stephen K AU - Wikel SK FAU - Kotsyfakis, Michail AU - Kotsyfakis M FAU - Pedra, Joao H F AU - Pedra JH LA - eng GR - K01 CK000101/CK/NCEZID CDC HHS/United States GR - R01 AI093653/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. DEP - 20121010 PL - England TA - Parasit Vectors JT - Parasites & vectors JID - 101462774 RN - 0 (Cytokines) RN - 0 (Immunologic Factors) SB - IM MH - Adult MH - Anaplasma phagocytophilum/*immunology MH - Animals MH - Cytokines/*antagonists & inhibitors/*metabolism MH - Humans MH - Immunologic Factors/metabolism MH - Ixodes/*immunology MH - Leukocytes, Mononuclear/drug effects/immunology MH - Macrophages/drug effects/immunology MH - Mice MH - Mice, Inbred C57BL MH - Saliva/*immunology PMC - PMC3503595 EDAT- 2012/10/12 06:00 MHDA- 2013/03/05 06:00 PMCR- 2012/10/10 CRDT- 2012/10/12 06:00 PHST- 2012/08/25 00:00 [received] PHST- 2012/10/06 00:00 [accepted] PHST- 2012/10/12 06:00 [entrez] PHST- 2012/10/12 06:00 [pubmed] PHST- 2013/03/05 06:00 [medline] PHST- 2012/10/10 00:00 [pmc-release] AID - 1756-3305-5-229 [pii] AID - 10.1186/1756-3305-5-229 [doi] PST - epublish SO - Parasit Vectors. 2012 Oct 10;5:229. doi: 10.1186/1756-3305-5-229.