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Distinctive TLR7 signaling, type I IFN production, and attenuated innate and adaptive immune responses to yellow fever virus in a primate reservoir host.
J Immunol. 2011 Jun 01; 186(11):6406-16.JI

Abstract

Why cross-species transmissions of zoonotic viral infections to humans are frequently associated with severe disease when viruses responsible for many zoonotic diseases appear to cause only benign infections in their reservoir hosts is unclear. Sooty mangabeys (SMs), a reservoir host for SIV, do not develop disease following SIV infection, unlike nonnatural HIV-infected human or SIV-infected rhesus macaque (RM) hosts. SIV infections of SMs are characterized by an absence of chronic immune activation, in association with significantly reduced IFN-α production by plasmacytoid dendritic cells (pDCs) following exposure to SIV or other defined TLR7 or TLR9 ligands. In this study, we demonstrate that SM pDCs produce significantly less IFN-α following ex vivo exposure to the live attenuated yellow fever virus 17D strain vaccine, a virus that we show is also recognized by TLR7, than do RM or human pDCs. Furthermore, in contrast to RMs, SMs mount limited activation of innate immune responses and adaptive T cell proliferative responses, along with only transient antiviral Ab responses, following infection with yellow fever vaccine 17D strain. However, SMs do raise significant and durable cellular and humoral immune responses comparable to those seen in RMs when infected with modified vaccinia Ankara, a virus whose immunogenicity does not require TLR7/9 recognition. Hence, differences in the pattern of TLR7 signaling and type I IFN production by pDCs between primate species play an important role in determining their ability to mount and maintain innate and adaptive immune responses to specific viruses, and they may also contribute to determining whether disease follows infection.

Authors+Show Affiliations

Emory University, Atlanta, GA 30329, USA. mark_feinberg@merck.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

21515797

Citation

Mandl, Judith N., et al. "Distinctive TLR7 Signaling, Type I IFN Production, and Attenuated Innate and Adaptive Immune Responses to Yellow Fever Virus in a Primate Reservoir Host." Journal of Immunology (Baltimore, Md. : 1950), vol. 186, no. 11, 2011, pp. 6406-16.
Mandl JN, Akondy R, Lawson B, et al. Distinctive TLR7 signaling, type I IFN production, and attenuated innate and adaptive immune responses to yellow fever virus in a primate reservoir host. J Immunol. 2011;186(11):6406-16.
Mandl, J. N., Akondy, R., Lawson, B., Kozyr, N., Staprans, S. I., Ahmed, R., & Feinberg, M. B. (2011). Distinctive TLR7 signaling, type I IFN production, and attenuated innate and adaptive immune responses to yellow fever virus in a primate reservoir host. Journal of Immunology (Baltimore, Md. : 1950), 186(11), 6406-16. https://doi.org/10.4049/jimmunol.1001191
Mandl JN, et al. Distinctive TLR7 Signaling, Type I IFN Production, and Attenuated Innate and Adaptive Immune Responses to Yellow Fever Virus in a Primate Reservoir Host. J Immunol. 2011 Jun 1;186(11):6406-16. PubMed PMID: 21515797.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Distinctive TLR7 signaling, type I IFN production, and attenuated innate and adaptive immune responses to yellow fever virus in a primate reservoir host. AU - Mandl,Judith N, AU - Akondy,Rama, AU - Lawson,Benton, AU - Kozyr,Natalia, AU - Staprans,Silvija I, AU - Ahmed,Rafi, AU - Feinberg,Mark B, Y1 - 2011/04/22/ PY - 2011/4/26/entrez PY - 2011/4/26/pubmed PY - 2011/8/13/medline SP - 6406 EP - 16 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 186 IS - 11 N2 - Why cross-species transmissions of zoonotic viral infections to humans are frequently associated with severe disease when viruses responsible for many zoonotic diseases appear to cause only benign infections in their reservoir hosts is unclear. Sooty mangabeys (SMs), a reservoir host for SIV, do not develop disease following SIV infection, unlike nonnatural HIV-infected human or SIV-infected rhesus macaque (RM) hosts. SIV infections of SMs are characterized by an absence of chronic immune activation, in association with significantly reduced IFN-α production by plasmacytoid dendritic cells (pDCs) following exposure to SIV or other defined TLR7 or TLR9 ligands. In this study, we demonstrate that SM pDCs produce significantly less IFN-α following ex vivo exposure to the live attenuated yellow fever virus 17D strain vaccine, a virus that we show is also recognized by TLR7, than do RM or human pDCs. Furthermore, in contrast to RMs, SMs mount limited activation of innate immune responses and adaptive T cell proliferative responses, along with only transient antiviral Ab responses, following infection with yellow fever vaccine 17D strain. However, SMs do raise significant and durable cellular and humoral immune responses comparable to those seen in RMs when infected with modified vaccinia Ankara, a virus whose immunogenicity does not require TLR7/9 recognition. Hence, differences in the pattern of TLR7 signaling and type I IFN production by pDCs between primate species play an important role in determining their ability to mount and maintain innate and adaptive immune responses to specific viruses, and they may also contribute to determining whether disease follows infection. SN - 1550-6606 UR - https://www.unboundmedicine.com/medline/citation/21515797/Distinctive_TLR7_signaling_type_I_IFN_production_and_attenuated_innate_and_adaptive_immune_responses_to_yellow_fever_virus_in_a_primate_reservoir_host_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=21515797 DB - PRIME DP - Unbound Medicine ER -