Jakob Michaelsson group
The main focus of our research is to investigate the differentiation, function and regulation of human Natural Killer (NK) cells during fetal development and in healthy adults, as well during viral infections.
Understanding how these cells develop and function during different stages of life, and during different conditions is important to achieve the long-term goal of our research, which is to aid in the development of new therapies in infectious diseases, cancer and transplantation. We continuously develop new techniques for advanced analysis of NK cells, and strive to be leading in flow cytometry analysis of human NK cells (currently 16-colour flow cytometry).
Keywords: NK cells, development, virus infection
Jakob Michaëlsson, group leader, PhD, Associate Professor
He was recruited to the Center for Infectious Medicine as a principal investigator in 2005, after 2 years as a postdoc at the Gladstone Institute of Virology and Immunology, University of California San Francisco. He received his PhD at the Karolinska Institute in 2002, with professor Klas Kärre as a supervisor.
Nicole Marquardt, PhD, Assistant Professor
Nicole completed her PhD in Hannover, Germany, in 2011, and got recruited to the Center for Infectious Medicine (CIM) in the same year. She has a long-standing expertise in the field of NK cell research both in mice and humans. At CIM, Nicole is focusing on human NK cells and other innate lymphoid cells (ILCs) in different fetal and adult tissues including the liver, uterus, and particularly the lung. Furthermore, Nicole is investigating the regulation of innate and adaptive lymphocytes in peripheral blood and tissues during acute viral infections.
Development of human NK cells in tissues
Little is known about how and where human NK cells develop and mature, and what signals are regulating NK cell development. Human NK cells have historically mainly been analyzed in the blood, and not in tissues. Only recently has it become apparent that NK cells distinct to those in peripheral blood can be detected in tissues. The overall aim of this project is to dissect fetal and adult NK cell development and function in tissues. In particular, we are investigating distinct tissue-resident NK cell populations in the adult lung, and aim at determining their role in lung diseases.
The role of NK cells in viral infections - model systems and chronic infections
NK cells are generally believed to be an important part of the immune response very early after infection. In order to study the earliest immune responses, including NK cell responses, to viral infections, we make use of a live, replicating, but attenuated vaccine (Yellow Fever vaccine) as a model. This approach allows us to study the immune response from before infection, through the earliest time points after infections to months after infection. Not only does this model allow us to investigate the earliest NK cell response in detail in a controlled fashion, but it also allows us to investigate correlates between different parts of the response, e.g. NK cells, T and B cells, and to define success factors for an efficient vaccine.
Epidemiological studies of NK cell receptors have demonstrated that NK cells are involved in conferring protection against HIV infection, as well as reducing viral load and slowing progression to AIDS. We are continuing our effort to understand the molecular basis for protection, as well as defining stronger correlates of immune protection in HIV, using a detailed analysis of NK cells in blood from patients with acute and chronic HIV infection.
Identification of a Human Natural Killer Cell Lineage-Restricted Progenitor in Fetal and Adult Tissues.
Immunity 2015 Aug;43(2):394-407
The Human NK Cell Response to Yellow Fever Virus 17D Is Primarily Governed by NK Cell Differentiation Independently of NK Cell Education.
J. Immunol. 2015 Oct;195(7):3262-72
Cutting edge: identification and characterization of human intrahepatic CD49a+ NK cells.
J. Immunol. 2015 Mar;194(6):2467-71
T-bet and Eomes are differentially linked to the exhausted phenotype of CD8+ T cells in HIV infection.
PLoS Pathog. 2014 Jul;10(7):e1004251
Activating killer cell Ig-like receptors in health and disease.
Front Immunol 2014 ;5():184
Tracing dynamic expansion of human NK-cell subsets by high-resolution analysis of KIR repertoires and cellular differentiation.
Eur. J. Immunol. 2014 Jul;44(7):2192-6
Invariant natural killer T cells developing in the human fetus accumulate and mature in the small intestine.
Mucosal Immunol 2014 Sep;7(5):1233-43
Differentiation and functional regulation of human fetal NK cells.
J. Clin. Invest. 2013 Sep;123(9):3889-901
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.
J. Immunol. 2013 Mar;190(5):2150-8
Rapid expansion and long-term persistence of elevated NK cell numbers in humans infected with hantavirus.
J. Exp. Med. 2011 Jan;208(1):13-21
Fetal and adult hematopoietic stem cells give rise to distinct T cell lineages in humans.
Science 2010 Dec;330(6011):1695-9
Education of human natural killer cells by activating killer cell immunoglobulin-like receptors.
Blood 2010 Feb;115(6):1166-74
Functionally distinct subsets of human NK cells and monocyte/DC-like cells identified by coexpression of CD56, CD7, and CD4.
Blood 2009 Nov;114(23):4823-31
Maternal alloantigens promote the development of tolerogenic fetal regulatory T cells in utero.
Science 2008 Dec;322(5907):1562-5
Immune reconstitution of CD56(dim) NK cells in individuals with primary HIV-1 infection treated with interleukin-2.
J. Infect. Dis. 2008 Jan;197(1):117-25
Human immunodeficiency virus type 1 (HIV-1)-specific CD8+ T(EMRA) cells in early infection are linked to control of HIV-1 viremia and predict the subsequent viral load set point.
J. Virol. 2007 Jun;81(11):5759-65
Regulation of T cell responses in the developing human fetus.
J. Immunol. 2006 May;176(10):5741-8
A signal peptide derived from hsp60 binds HLA-E and interferes with CD94/NKG2A recognition.
J. Exp. Med. 2002 Dec;196(11):1403-14
We are always interested in getting in touch with talented and highly motivated potential co-workers. If you are interested in doing research within our group, please contact the group leader Jakob Michaëlsson.