Johan Sandberg group

Cellular immune responses play an important role in protection from viral infections. These responses can also, however, contribute to the immunopathogenesis of chronic viral infections such as human immunodeficiency virus (HIV)-1 and hepatitis C virus (HCV) infections.

Another aspect of the complex relationship between host and pathogen is that most viruses have developed immune evasive mechanisms to avoid detection and elimination by the host cellular immune responses. Our research aims at understanding the nature and balance between protection, pathology and immune evasion during acute and chronic stages of viral infections.

We are particularly interested in HIV-1 infection, but we also study aspects of other chronic viral infections such as HCV and herpes simplex virus (HSV) where immune evasion mechanisms are significant. Another layer of complexity is added by vaccines, antiviral and immunomodulatory treatments used today and in development. These we bring in to our studies to learn lessons about the treatments as such, as well as about the basic immunology that we can learn from how the immune system responds to such treatments.

Keywords: T cells, NK cells, NKT cells, MAIT cells, CD1d, MR1

Members

Johan K. Sandberg, PhD, Professor, Group leader. Mobile phone: +46-70 7930885

Edwin Leeansyah, PhD, Assistant Professor.
I joined Johan Sandberg's group as a postdoc in 2010 to study MAIT cells development and functional heterogeneity in humans, and the role of MAIT cells in chronic viral infections. I'm currently based at Program in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore. In my present work, I seek to understand how MAIT cells distinguish pathogenic bacteria from the commensal microbiota, and their roles during the course of bacterial infections.

Jean-Baptiste Gorin, PhD, Postdoctoral Fellow
After obtaining my PhD on the effect of radiation on the immune response to cancer at the University of Nantes in 2013, I decided to study the immune system in a different setting and recently joined Johan Sandberg’s group to investigate MAIT cell dysfunction in chronic viral infections.

Tiphaine Parrot, PhD, Postdoctoral Fellow
I obtained my PhD in 2016 at the University of Nantes in France, where I investigated the function and the origin of the CD4+CD8+ double positive T cell population infiltrating melanoma skin cancer. My interest in T cell responses and biology led me to join Johan Sandberg´s group in 2017 to explore MAIT cells in hepatitis B virus infection and liver cancer.

Caroline Boulouis, PhD student
I am doctor of pharmacy, graduated from the University of
Montpellier, in the South of France. I joined Johan Sandberg's group early 2016 to study MAIT cell in context of bacterial infection.

Kerri Lal, PhD student
I am a doctoral student that joined the Sandberg lab in 2015, and conduct a majority of my research in Washington, D.C. at the U.S. Military HIV Research Program. My project seeks to understand the role of MAIT cells in acute HIV infection by measuring changes in phenotype, functionality, and the transcriptional profile of these cells at different stages in acute infection.

Johanna Emgård, PhD student
Johanna received her Master’s degree in Biomedical Sciences from the Hebrew University of Jerusalem, Israel, in 2016. Her thesis work described a mechanism by which the oral pathogen Fusobacterium nucleatum colonizes colorectal tumors. In her spare time she illustrates plants and birds and has previously published the book Humlesjös Flora (2009). She also enjoys hiking and cross country skiing.

Projects

Invariant T cell populations in health and viral disease

The first broad aim of our research efforts is to understand the role that invariant T cell populations play during viral infections. Here we focus on two types of cells: the invariant natural killer T (NKT) cells, and the mucosa-associated invariant T (MAIT) cells. These cells recognize antigen presented by the non-polymorphic and evolutionarily conserved MHC-like molecules CD1d and MR1, respectively. These molecules present endogenous or pathogen-derived antigens to rapidly activate NKT and MAIT cells in an innate-like fashion. We are investigating the protective and immune-pathogenic role these cell types play during infections with three different viruses: HIV-1, HCV, and HSV.

Qualitative aspects of successful and unsuccessful CD8 T cell responses

In a second broad aim we want to understand specific aspects of the human CD8 T cell response to viral infection. We are investigating the live attenuated yellow fever virus (YFV) vaccine as a model for acute viral infection, and study the evolution of the YFV-specific T cell response in humans. The YFV vaccine gives good protection and the response induced can be viewed as an example of successful immune response. The opposite can be said about HIV infection where, in the long run, the T cell response is unsuccessful. Here we investigate differences in T cell responses between infection with viral subtypes that differ with regard to disease progression.

Natural killer cells in viral disease

In a third broad aim we examine the role of NK cell responses during viral infection, notably HIV-1 and HCV infections. One focus here is the genesis and role of aberrant populations of NK cells in these infections. Another focus is the cause and consequence of receptor repertoire changes in NK cells during these infections.

Chronic immune activation in HIV-1 pathogenesis

Persistent immune activation is recognized as a major driver of HIV-1 pathogenesis. The mechanisms involved are still not fully understood, and here we aim to help clarify the role that adaptive and innate immune responses play in the pathologic immune activation. We are also investigating the role of co-infections in this context, with a particular focus on the role that HCV might play in HIV-1 infected patients.

Financial support:

  • The Swedish Research Council
  • The Swedish Cancer Society
  • The US National Institutes of Health
  • The Swedish Medical Doctors Against AIDS Foundation
  • In addition, group members hold fellowships from Karolinska Institutet and the Canadian Institutes for Health Research

Collaborations:

  • University of California
  • US Military HIV Research Program
  • Makerere University
  • University of Sao Paulo
  • Case Western Reserve University
  • The George Washington University
  • as well as several other national and international collaborators

Selected publications

Human MAIT cell cytolytic effector proteins synergize to overcome carbapenem resistance in Escherichia coli.
Boulouis C, Sia WR, Gulam MY, Teo JQM, Png YT, Phan TK, et al
PLoS Biol. 2020 06;18(6):e3000644

Dynamic MAIT cell response with progressively enhanced innateness during acute HIV-1 infection.
Lal KG, Kim D, Costanzo MC, Creegan M, Leeansyah E, Dias J, et al
Nat Commun 2020 01;11(1):272

MAIT Cells Are Major Contributors to the Cytokine Response in Group A Streptococcal Toxic Shock Syndrome.
Emgård J, Bergsten H, McCormick JK, Barrantes I, Skrede S, Sandberg JK, et al
Proc. Natl. Acad. Sci. U.S.A. 2019 12;116(51):25923-25931

The viral protein corona directs viral pathogenesis and amyloid aggregation.
Ezzat K, Pernemalm M, Pålsson S, Roberts TC, Järver P, Dondalska A, et al
Nat Commun 2019 05;10(1):2331

The CD4-CD8- MAIT cell subpopulation is a functionally distinct subset developmentally related to the main CD8+ MAIT cell pool.
Dias J, Boulouis C, Gorin JB, van den Biggelaar RHGA, Lal KG, Gibbs A, et al
Proc. Natl. Acad. Sci. U.S.A. 2018 12;115(49):E11513-E11522

Chronic hepatitis delta virus infection leads to functional impairment and severe loss of MAIT cells.
Dias J, Hengst J, Parrot T, Leeansyah E, Lunemann S, Malone DFG, et al
J. Hepatol. 2019 Aug;71(2):301-312

Terminal Effector CD8 T Cells Defined by an IKZF2+IL-7R- Transcriptional Signature Express FcγRIIIA, Expand in HIV Infection, and Mediate Potent HIV-Specific Antibody-Dependent Cellular Cytotoxicity.
Naluyima P, Lal KG, Costanzo MC, Kijak GH, Gonzalez VD, Blom K, et al
J. Immunol. 2019 Oct;203(8):2210-2221

Identification and characterization of HIV-specific resident memory CD8+ T cells in human lymphoid tissue.
Buggert M, Nguyen S, Salgado-Montes de Oca G, Bengsch B, Darko S, Ransier A, et al
Sci Immunol 2018 06;3(24):

Severely Impaired Control of Bacterial Infections in a Patient With Cystic Fibrosis Defective in Mucosal-Associated Invariant T Cells.
Pincikova T, Paquin-Proulx D, Moll M, Flodström-Tullberg M, Hjelte L, Sandberg JK
Chest 2018 05;153(5):e93-e96

Limited immune surveillance in lymphoid tissue by cytolytic CD4+ T cells during health and HIV disease.
Buggert M, Nguyen S, McLane LM, Steblyanko M, Anikeeva N, Paquin-Proulx D, et al
PLoS Pathog. 2018 04;14(4):e1006973

Bacterial deception of MAIT cells in a cloud of superantigen and cytokines.
Sandberg JK, Norrby-Teglund A, Leeansyah E
PLoS Biol. 2017 Jul;15(7):e2003167

Multiple layers of heterogeneity and subset diversity in human MAIT cell responses to distinct microorganisms and to innate cytokines.
Dias J, Leeansyah E, Sandberg JK
Proc. Natl. Acad. Sci. U.S.A. 2017 07;114(27):E5434-E5443

Human MAIT-cell responses to Escherichia coli: activation, cytokine production, proliferation, and cytotoxicity.
Dias J, Sobkowiak MJ, Sandberg JK, Leeansyah E
J. Leukoc. Biol. 2016 07;100(1):233-40

Innate Invariant NKT Cell Recognition of HIV-1-Infected Dendritic Cells Is an Early Detection Mechanism Targeted by Viral Immune Evasion.
Paquin-Proulx D, Gibbs A, Bächle SM, Checa A, Introini A, Leeansyah E, et al
J. Immunol. 2016 09;197(5):1843-51

MAIT cells reside in the female genital mucosa and are biased towards IL-17 and IL-22 production in response to bacterial stimulation.
Gibbs A, Leeansyah E, Introini A, Paquin-Proulx D, Hasselrot K, Andersson E, et al
Mucosal Immunol 2017 01;10(1):35-45

Involvement of a C-terminal motif in the interference of primate lentiviral Vpu proteins with CD1d-mediated antigen presentation.
Bächle SM, Sauter D, Sibitz S, Sandberg JK, Kirchhoff F, Moll M
Sci Rep 2015 Apr;5():9675

Arming of MAIT Cell Cytolytic Antimicrobial Activity Is Induced by IL-7 and Defective in HIV-1 Infection.
Leeansyah E, Svärd J, Dias J, Buggert M, Nyström J, Quigley MF, et al
PLoS Pathog. 2015 Aug;11(8):e1005072

HIV Type 1 Disease Progression to AIDS and Death in a Rural Ugandan Cohort Is Primarily Dependent on Viral Load Despite Variable Subtype and T-Cell Immune Activation Levels.
Eller MA, Opollo MS, Liu M, Redd AD, Eller LA, Kityo C, et al
J. Infect. Dis. 2015 May;211(10):1574-84

Invariant natural killer T cells developing in the human fetus accumulate and mature in the small intestine.
Loh L, Ivarsson MA, Michaëlsson J, Sandberg JK, Nixon DF
Mucosal Immunol 2014 Sep;7(5):1233-43

Impaired natural killer cell responses are associated with loss of the highly activated NKG2A(+)CD57(+)CD56(dim) subset in HIV-1 subtype D infection in Uganda.
Naluyima P, Eller MA, Laeyendecker O, Quinn TC, Serwadda D, Sewankambo NK, et al
AIDS 2014 Jun;28(9):1273-8

The Human NK Cell Response to Yellow Fever Virus 17D Is Primarily Governed by NK Cell Differentiation Independently of NK Cell Education.
Marquardt N, Ivarsson MA, Blom K, Gonzalez VD, Braun M, Falconer K, et al
J. Immunol. 2015 Oct;195(7):3262-72

Acquisition of innate-like microbial reactivity in mucosal tissues during human fetal MAIT-cell development.
Leeansyah E, Loh L, Nixon DF, Sandberg JK
Nat Commun 2014 ;5():3143

Will loss of your MAITs weaken your HAART [corrected]?
Sandberg JK, Dias J, Shacklett BL, Leeansyah E
AIDS 2013 Oct;27(16):2501-4

Soluble biomarkers of HIV transmission, disease progression and comorbidities.
Leeansyah E, Malone DF, Anthony DD, Sandberg JK
Curr Opin HIV AIDS 2013 Mar;8(2):117-24

IVIg immune reconstitution treatment alleviates the state of persistent immune activation and suppressed CD4 T cell counts in CVID.
Paquin-Proulx D, Santos BA, Carvalho KI, Toledo-Barros M, Barreto de Oliveira AK, Kokron CM, et al
PLoS ONE 2013 ;8(10):e75199

Dysregulated CD1 profile in myeloid dendritic cells in CVID is normalized by IVIg treatment.
Paquin-Proulx D, Santos BA, Carvalho KI, Toledo-Barros M, Oliveira AK, Kokron CM, et al
Blood 2013 Jun;121(24):4963-4

Differential loss of invariant natural killer T cells and FoxP3⁺ regulatory T cells in HIV-1 subtype A and subtype D infections.
Flach B, Naluyima P, Blom K, Gonzalez VD, Eller LA, Laeyendecker O, et al
J. Acquir. Immune Defic. Syndr. 2013 Jul;63(3):289-93

Temporal dynamics of the primary human T cell response to yellow fever virus 17D as it matures from an effector- to a memory-type response.
Blom K, Braun M, Ivarsson MA, Gonzalez VD, Falconer K, Moll M, et al
J. Immunol. 2013 Mar;190(5):2150-8

Activation, exhaustion, and persistent decline of the antimicrobial MR1-restricted MAIT-cell population in chronic HIV-1 infection.
Leeansyah E, Ganesh A, Quigley MF, Sönnerborg A, Andersson J, Hunt PW, et al
Blood 2013 Feb;121(7):1124-35

 

Open positions
We always want to get in touch with talented potential co-workers. If you are interested in doing research within our group, as a degree project or as a researcher, please contact the group leader Johan Sandberg.
Open positions