Gunilla Källenius

Gunilla Källenius

Professor | Docent
Visiting address: B2:03, Karolinska Universitetssjukhuset Solna, 17176 Solna
Postal address: K2 Medicin, Solna, K2 Infekt Färnet A Sundling C, 171 77 Stockholm
Part of:

About me

  • I am a Professor in clinical Microbiology, with a broad background in tuberculosis research, specifically in diagnostics and vaccine development. I graduated as a medical doctor from Uppsala University 1970, and received a Ph.D. at Karolinska Institutet 1981, After clinical work in paediatrics and infectious diseases in Uppsala and Stockholm I held a postdoc position at the Swedish Medical Research Council 1982-84. Between 1985 and 2009 I worked at the Swedish Institute for Infectious Disease Control.

Research

  • My early publications dealt with the pathogenesis of urinary tract infections caused by E.coli. I was first to show that E.coli isolated from patients with acute pyelonephritis bound to uroepithelial cells in a manner that strongly correlated with their binding to human erythrocytes and that the binding to erythrocytes was dependent on the presence of P blood group antigens on the surface of the erythrocytes. I, with co-workers, was also first to identify the molecular structure of the human receptor active structure (-D-Galp-(1-4)--D-Galp) on erythrocytes and human uroepithelial cells. This binding was mediated by fimbriae on E. coli, which made us name them P-fimbriae. We found that most E.coli strains causing pyelonephritis in children and adults possessed P fimbriae. In collaboration with James Roberts, Tulane University, we showed that P-fimbriated E.coli can cause pyelonephritis in the non-human primate, with a disease course very similar to the disease in man, and that the infection could be prevented by a soluble receptor analogue, concluding that P-fimbriae are an important virulence factor in the initiation of pyelonephritis.

    a. Källenius G, Möllby R, Svenson S B, Winberg J, Lundblad A, Svensson S &
  • Cedergren B: The pk antigen as receptor for the haemagglutinin of pyelonephritic Escherichia coli. FEMS Microbiology Letters 7:297-302, 1980.
    b. Källenius G, Svenson S B, Möllby R, Cedergren B, Hultberg H &
  • Winberg J: Structure of carbohydrate part of receptor on human uroepithelial cells for pyelonephritogenic Escherichia coli. Lancet ii:604-606, 1981.
    c. Källenius G, Möllby R, Svenson S B, Helin I, Hultberg H, Cedergren B &
  • Winberg J: Occurrence of P-fimbriated Escherichia coli in urinary tract infections. Lancet ii:1369-72, 1981.
    d. Tullus K, Hörlin K, Svenson S B &
  • Källenius G: Epidemic outbreaks of acute pyelonephritis caused by nosocomial spread of P-fimbriated E.coli in children. J Inf Dis, 150:728-736, 1984.

    In the 1980s I turned my research interest to tuberculosis, an underexplored research area at that time. Together with Stefan Svenson we used our knowledge of microbial glycolipids to explore the role of the Mycobacterium tuberculosis (M.tb) glycolipid lipoarabinomannan (LAM) in the diagnosis and prevention of tuberculosis. We developed monoclonal antibodies to LAM to show for the first time that tuberculosis could be diagnosed by detection of LAM in urine. These studies have laid the groundwork for the development of commercial tests for tuberculosis based on the detection of LAM in urine. So far these test have low sensitivity, and I am still working on the advancement of new technologies to reach the sensitivity needed.

    a. Hamasur B, Bruchfeld J, Haile M, Bjorvatn B, Källenius G, Svenson S B. Rapid diagnosis of tuberculosis by detection of mycobacterial arabinomannan in urine. J. Microbiol. Meth. 2001 45:41-52

  • doi: 10.1016/s0167-7012(01)00239-1
    b. Hamasur B, Bruchfeld J, van Helden P, Källenius G, Svenson S. A sensitive urinary lipoarabinomannan test for tuberculosis. (2015). A Sensitive Urinary Lipoarabinomannan Test for Tuberculosis. PLoS ONE 10(4): e0123457. doi:10.1371/journal.pone.0123457
    c. Correia-Neves M, Fröberg G, Korshun L, Viegas S, Vaz P, Ramanlal N, Bruchfeld J, Hamasur B, Brennan P, Källenius G.. Biomarkers for Tuberculosis: The Case for Lipoarabinomannan. ERJ Open Res. 2019 Feb 11
  • 5(1). pii: 00115-2018. doi: 10.1183/23120541.00115-2018.
    d. Cantera JL, Lillis LM, Peck RB, Moreau E, Schouten JA, Davis P, Drain PK, Andama A, Pinter A, Kawasaki M, Källenius G, Sundling G, Dobos KM, Flores D, Chatterjee D, Murphy E, Halas OR, Boyle DS. Performance of novel antibodies for lipoarabinomannan to develop diagnostic tests for Mycobacterium tuberculosis 2022 Sep 30
  • 17(9):e0274415. doi: 10.1371/journal.pone.0274415.

    Stefan Svenson and I also used our knowledge of mycobacterial glycoconjugates to study the role of LAM in the prevention of tuberculosis. We constructed a series of monoclonal antibodies, and published the very first paper on a monoclonal antibody against LAM that protected against experimental Mtb infection. We also developed lipoarabinomannan specific oligosaccharide-protein conjugates that resulted in the very first paper on the construction and protective effect of an arabinomannan (AM)-protein conjugate vaccine candidate against tuberculosis. The last decades the main interest in, and funding of, the development of tuberculosis vaccine candidates has been dominated by either protein/peptide based candidates or live vaccines. However more recently there is a renewed interest in the potential role of carbohydrate conjugates in vaccine development, and my present research connects to this.

    a. Hamasur B, Källenius G, Svenson SB. Synthesis and immunologic characterization of Mycobacterium tuberculosis lipoarabinomannan specific oligosaccharide-protein conjugates. Vaccine, 17:2853-61, 1999. doi: 10.1016/s0264-410x(99)00124-3
    b. Hamasur B, Haile M, Pawlowski A, Schröder U, Williams A, Hatch G, Hall G, Marsh P, Källenius G, Svenson SB. Mycobacterium tuberculosis arabinomannan-protein conjugates protect against tuberculosis. Vaccine. 2003 21:4081-93
  • 2003. doi: 10.1016/s0264-410x(03)00274-3
    c. Hamasur B, Haile M, Pawlowski A, Schroder U, Kallenius G, Svenson SB. A mycobacterial lipoarabinomannan specific monoclonal antibody and its F(ab´) fragment prolong survival of mice infected with Mycobacterium tuberculosis. Clin Exp Immunol. 2004 Oct
  • 138(1):30-8. doi: 10.1111/j.1365-2249.2004.02593.x
    d. Källenius G, Nigou, Cooper A, Correia-Neves M. Mycobacterial Glycolipids - Role in Immunomodulation and Targets for Vaccine Development Front. Immunol. 11(2020) 2620. PMID: 33133110

    My interest in One Health has resulted in long term collaborations with colleagues in Sub-Saharan Africa. The research has been focused on the molecular epidemiology of human and bovine TB, caused by M.tb and Mycobacterium bovis (M.bovis) respectively. In large collaborative studies we have identified particular lineages of Mtb and M. bovis that are spread in Africa. With colleagues and students in Mozambique I have explored the zoonotic aspects of TB. We have identified a district (Govuro) where the prevalence of bovine TB is extremely high, with about 40% of cattle infected, and in individual herds up to 70% . Here we are exploring the mechanisms of transmission of M. bovis to humans, and the innate and adaptive immune responses that are elicited upon continuous exposure to M. bovis upon drinking infected milk or handling infected cattle carcasses.

    a. Machado A, Rito T, Ghebremichael S, Muhate N, Maxhuza G, Macuamule C, Moiane I, Macucule B, Marranangumbe AS, Baptista J, Manguele J, Koivula T, Streicher EM, Muller A, Warren RM, Kallenius G, van Helden P, Correia-Neves M. Genetic diversity and potential routes of transmission of Mycobacterium bovis in Mozambique. PLoS Negl Trop Dis. 2018 Jan 18
  • 12(1). doi: 10.1371/journal.pntd.0006147

    b. Viegas SO, Ghebremichael S, Massawo L, Alberto M, Fernandes FC, Monteiro E, Couvin D, Matavele JM, Rastogi N, Correia-Neves M, Machado A, Carrilho C, Groenheit R, Källenius G, Koivula T. Mycobacterium tuberculosis causing tuberculous lymphadenitis in Maputo, Mozambique. BMC Microbiol. 2015 Nov 21
  • 15(1):268. doi: 10.1186/s12866-015-0603-5.

    c. Moiane I, Machado A, Santos N, Nhambir A, Inlamea, O, Hattendorf, J. Källenius G, Zinnstag J, Correia-Neves M. Prevalence of Bovine Tuberculosis and Risk Factor Assessment in Cattle in Rural Livestock Areas of Govuro District in the Southeast of Mozambique. PLoS One. 2014 Mar 14
  • 9(3):e91527. doi: 10.1371/journal.pone.0091527.

    d. Viegas SO, Machado A, Groenheit R, Ghebremichael S, Pennhag A, Gudo PS, Cuna Z, Langa E, Miotto P, Cirillo DM, Rastogi N, Warren RM, van Helden PD, Koivula T, Källenius G. Mycobacterium tuberculosis Beijing genotype is associated with HIV infection in Mozambique. PLoS One. 2013 Aug 7
  • 8(8):e71999.


    5. More recently my interest in host-pathogen interactions made me explore latent tuberculosis (defined by WHO as a state of persistent immune response to stimulation by Mtb antigens without evidence of clinically manifested active TB) in relation to Mtb glycolipids. We had previously observed that LAM, and its related glycolipids, induce divergent and opposing immune responses on monocytes and dendritic cells. Now we found that myeloid cells in Mtb-immunoreactive individuals respond with a dampened cytokine response following stimulation with the Mtb glycolipids LAM and its precursor, phosphatidyl-myo-inositol mannoside (PIM). This observation suggests that innate hyporesponsiveness, or tolerance, to glycolipids could be an important mechanism of how Mtb-immunoreactive individuals are protected from disease. These studies give the rationale for my present research where I will explore in depth the mechanisms of tolerance to the glycolipids LAM and PIM and explore how this correlates with Mtb control.

    a. Källenius G, Correia-Neves M, Buteme H, Hamasur B, Svenson SB. Lipoarabinomannan, and its related glycolipids, induce divergent and opposing immune responses to Mycobacterium tuberculosis depending on structural diversity and experimental variations. Tuberculosis. (Edinb). 2015 Oct 28. pii: S1472-9792(15)30090-1. PMID: 26586646
    b. Correia-Neves M, Sundling C, Cooper A, Källenius G. Lipoarabinomannan in Active and Passive Protection Against Tuberculosis. Front Immunol. 2019 Sep 11
  • 10:1968 PMID: 31572351
    c. Silva CS, Sundling C, Folkesson E, Fröberg G, Nobrega C, Canto-Gomes J, Chambers BJ, Lakshmikanth T, Brodin P, Bruchfeld J, Nigou J, Correia-Neves M, Källenius G. High Dimensional Immune profiling Reveals Different Response Patterns in Active and Latent Tuberculosis Following Stimulation with Mycobacterial Glycolipids. Front. Immunol. 23 November 2021 PMID: 34887849
    d. Correia-Neves M, Nigou J, Mousavian Z, Sundling S, Källenius G. Immunological hyporesponsiveness in tuberculosis: The role of mycobacterial glycolipids. Front. Immunol. 2022 Dec 2
  • 13:1035122. PMID: 36544778

Articles

All other publications

Grants

Employments

  • Professor, Department of Medicine, Karolinska Institutet, 2020-2024

Degrees and Education

  • Docent, Karolinska Institutet, 1985

News from KI

Events from KI