The innate immune system is rapidly responding to defend against incoming pathogens. Our research is aiming to explore pathogen interaction with host cell signaling, and its correlation with subversion or induction of protective innate responses. The overall aim is to study early innate immune responses against virus infections to reveal early biomarkers and novel therapeutic targets. We are in particular interested in responses engaged after Toll-like-receptor signaling and after contact with apoptotic cells. The aim with these projects is to enhance the understanding of early innate mechanisms during infections or tissue damage with the dendritic cell in focus. This knowledge will contribute to novel approaches of immune modeling during immune pathogenesis and the development of vaccine adjuvants, where the activation of dendritic cells has emerged as a key event in shaping the following adaptive immune responses.

 

Key words: Dendritic cell, TLR, apoptotic cell, cytokines, host restriction factors, HIV-1, RSV, TBEV, influenza.

 

 

Selected publications

Uchtenhagen H, Schiffner T, Bowles E, Heyndrickx L, LaBranche C, Applequist SE, Jansson M, De Silva T, Back JW, Achour A, Scarlatti G, Fomsgaard A, Montefiori D, Stewart-Jones G, Spetz AL. Boosting of HIV-1 Neutralizing Antibody Responses by a Distally Related Retroviral Envelope Protein. J Immunol. 2014 Jun 15;192(12):5802-12.

Mohanram V, Sköld AE, Bächle SM, Pathak SK, Spetz AL. (2013) IFN-α induces APOBEC3G, F, and A in immature dendritic cells and limits HIV-1 spread to CD4+ T cells. J Immunol. 190(7):3346-53.

Sköld AE, Hasan M, Vargas L, Saidi H, Bosquet N, Le Grand R, Smith CI, Spetz AL. (2012) Single-stranded DNA oligonucleotides inhibit TLR3-mediated responses in human monocyte-derived dendritic cells and in vivo in cynomolgus macaques. Blood.120(4):768-77.

Pathak SK, Sköld AE, Mohanram V, Persson C, Johansson U, Spetz AL. (2012) Activated apoptotic cells induce dendritic cell maturation via engagement of Toll-like receptor 4 (TLR4), dendritic cell-specific intercellular adhesion molecule 3 (ICAM-3)-grabbing nonintegrin (DC-SIGN), and β2 integrins. J Biol Chem. 287(17):13731-42.

Mohanram V, Johansson U, Sköld AE, Fink J, Kumar Pathak S, Mäkitalo B, Walther-Jallow L, Spetz AL. (2011) Exposure to apoptotic activated CD4+ T cells induces maturation and APOBEC3G-mediated inhibition of HIV-1 infection in dendritic cells. PLoS One. 6(6):e21171.

Ozkaya Sahin G, Bowles EJ, Parker J, Uchtenhagen H, Sheik-Khalil E, Taylor S, Pybus OG, Mäkitalo B, Walther-Jallow L, Spångberg M, Thorstensson R, Achour A, Fenyö EM, Stewart-Jones GB, Spetz AL. (2010) Generation of neutralizing antibodies and divergence of SIVmac239 in cynomolgus macaques following short-term early antiretroviral therapy. PLoS Pathog. 6(9):e1001084.

 

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