Research group Bergman - The AMP-group

The group works broadly to understand the immune system in various infectious conditions, with a focus on respiratory tract infections (pneumococcus, tuberculosis, SARS CoV-2/COVID-19). We use various model systems in human cells and zebrafish. We also study cells from patients with different immunodeficiency conditions. During the pandemic, we have worked on many projects about COVID-19 in patients with primary immunodeficiency.

The group works with two main lines. One line relates to patients with primary immunodeficiency, where we search for underlying mechanisms that can explain increased susceptibility to infection. We start with a thorough clinical and immunological investigation and often continue with whole genome sequencing. Sometimes we find a genetic cause for the patient's problem. With this knowledge, we can recreate the mutation in various experimental systems, e.g. cells or zebrafish, which can then be infected with the same microbe that made the patient sick. This methodology allows us to study human diseases in detail and learn more that can form the basis for new diagnostics, treatment or prevention. We have extensive and close collaboration with other research groups at KI and abroad in this field, which is important for gaining access to the newest technologies.

The second line of research is based on knowledge of natural immunity and antimicrobial peptides (AMP), which we have now studied for more than 20 years. We are developing a new concept for treating infections, so-called "Host Directed Therapy". The concept is about not only attacking the bacteria with antibiotic drugs, but also increasing the endogenous immune system. We have specifically targeted AMPs, which are small peptides that are formed in the body's mucous membranes and by immune cells. AMPs kill bacteria and viruses directly but also by activating and recruiting various immune cells to the site of an infection (chemotaxis). We have discovered that vitamin D and Phenylbutyrate (PBA), together greatly increase the production of AMPs and contribute to better killing of mycobacteria in macrophages. Our goal is to identify new and more potent substances to increase the production of AMPs and how the expression of AMPs is regulated under normal conditions but also how to boost or block these systems with various drugs.

The overaching goal is to develop "Host Directed Therapy" as a new treatment against infections by experimental studies in the laboratory but also through clinical trials on patients with infectious diseases.

Research group leader Peter Bergman

Peter Bergman

Professor/senior physician
08-524 837 18
H5 Department of Laboratory Medicine

Our research in the media

Primary Immunodeficiency and Covid-19

Peter Bergman is interviewed by Malou on TV4 about severe Covid-19 in a previously healthy person (the project is presented):

Part 1 (October 2020)

https://www.youtube.com/watch?v=giMVtSIPqy8

Peter Bergman follows up and explains with the genetic investigation found in the patient.

Part 2 (March 2021)

https://www.youtube.com/watch?v=KOUhSl_eK5o

Host Directed Therapy

Ongoing projects

These projects are ongoing in close collaboration with several other research groups at KI.

  • Genetic vulnerability in severe Covid-19 infection (the COVPID study)
  • Vaccine response in immunosuppressed patients (COVAXID trial)
  • Covid-19 in patients with primary immunodeficiency – a national registry study (PIDREG study)
  • Regulation and activation of antimicrobial peptides in tuberculosis and infections caused by atypical mycobacteria.
  • Post-translational modification of AMP as a new regulatory mechanism in inflammatory skin diseases
  • Activation of AMP as a new infection treatment, so-called "Host Directed Therapy"
  • Chronic stress and the immune system - experimental and clinical studies
  • Vitamin D and respiratory tract infections – experimental and clinical studies.
  • Vitamin D and immunity in cancer patients in palliative care.

Group members

Siméon Beau

Erasmus student

Alumni

Samuel Paulson

Avinash Padhi

Harpa Karadottir

Salma Al-Adwani

Catharina Missailidis

Monica Lindh

Maarten Coorens

Frank Nylén

Erica Miraglia

Min Wan

Research techniques

  • Cell culture
  • Work with biological samples from patients
  • Confocal microscopy
  • qPCR
  • Western blot analysis
  • Microbiological work with bacteria and fungi
  • HPLC
  • LC-MS/MS
  • Circular dichroism
  • ChIP assay
  • Flow cytometry
  • Model system in zebrafish

External funding

The Swedish Research Council, CIMED, Heart-Lung Foundation, Stockholm County Council (ALF), Karolinska Institutet, Horizon 2020 (EU consortium).

Teaching assignments

We regularly teach at the Medical Program, the Dental Program, the BMA program and several other programs at KI as well as in various postgraduate courses, mainly in microbiology, immunology and infection biology.

Selected publications (2021-2022)

Primary immunodeficiency, Covid-19

Three Adult Cases of STAT1 Gain-of-Function with Chronic Mucocutaneous Candidiasis Treated with JAK Inhibitors.
Borgström EW, Edvinsson M, Pérez LP, Norlin AC, Enoksson SL, Hansen S, Fasth A, Friman V, Kämpe O, Månsson R, Estupiñán HY, Wang Q, Ziyang T, Lakshmikanth T, Smith CIE, Brodin P, Bergman P
J Clin Immunol 2023 Jan;43(1):136-150

Ancestral SARS-CoV-2-specific T cells cross-recognize the Omicron variant.
Gao Y, Cai C, Grifoni A, Müller TR, Niessl J, Olofsson A, Humbert M, Hansson L, Österborg A, Bergman P, Chen P, Olsson A, Sandberg JK, Weiskopf D, Price DA, Ljunggren HG, Karlsson AC, Sette A, Aleman S, Buggert M
Nat Med 2022 Mar;28(3):472-476

Do reduced numbers of plasmacytoid dendritic cells contribute to the aggressive clinical course of COVID-19 in chronic lymphocytic leukaemia?
Smith CIE, Zain R, Österborg A, Palma M, Buggert M, Bergman P, Bryceson Y
Scand J Immunol 2022 Apr;95(4):e13153

Elevated CD21low B Cell Frequency Is a Marker of Poor Immunity to Pfizer-BioNTech BNT162b2 mRNA Vaccine Against SARS-CoV-2 in Patients with Common Variable Immunodeficiency.
Bergman P, Wullimann D, Gao Y, Wahren Borgström E, Norlin AC, Lind Enoksson S, Aleman S, Ljunggren HG, Buggert M, Smith CIE
J Clin Immunol 2022 May;42(4):716-727

Estimating the number of diseases - the concept of rare, ultra-rare, and hyper-rare.
Smith CIE, Bergman P, Hagey DW
iScience 2022 Aug;25(8):104698

Immunodeficiency syndromes differentially impact the functional profile of SARS-CoV-2-specific T cells elicited by mRNA vaccination.
Gao Y, Cai C, Wullimann D, Niessl J, Rivera-Ballesteros O, Chen P, Lange J, Cuapio A, Blennow O, Hansson L, Mielke S, Nowak P, Vesterbacka J, Akber M, Perez-Potti A, Sekine T, Müller TR, Boulouis C, Kammann T, Parrot T, Muvva JR, Sobkowiak M, Healy K, Bogdanovic G, Muschiol S, Söderdahl G, Österborg A, Hellgren F, Grifoni A, Weiskopf D, Sette A, Loré K, Sällberg Chen M, Ljungman P, Sandberg JK, Smith CIE, Bergman P, Ljunggren HG, Aleman S, Buggert M
Immunity 2022 Sep;55(9):1732-1746.e5

Mutation in the TACI gene and autoimmune neutropenia: A case report.
Bergman P, Broliden PA, Ratcliffe P, Lourda M, Flesch B, Höglund P, Palmblad J
Am J Hematol 2022 Jun;97(6):E207-E210

Neutralizing SARS-CoV-2 Antibodies in Commercial Immunoglobulin Products Give Patients with X-Linked Agammaglobulinemia Limited Passive Immunity to the Omicron Variant.
Lindahl H, Klingström J, Da Silva Rodrigues R, Christ W, Chen P, Ljunggren HG, Buggert M, Aleman S, Smith CIE, Bergman P
J Clin Immunol 2022 Aug;42(6):1130-1136

NK cell frequencies, function and correlates to vaccine outcome in BNT162b2 mRNA anti-SARS-CoV-2 vaccinated healthy and immunocompromised individuals.
Cuapio A, Boulouis C, Filipovic I, Wullimann D, Kammann T, Parrot T, Chen P, Akber M, Gao Y, Hammer Q, Strunz B, Pérez Potti A, Rivera Ballesteros O, Lange J, Muvva JR, Bergman P, Blennow O, Hansson L, Mielke S, Nowak P, Söderdahl G, Österborg A, Smith CIE, Bogdanovic G, Muschiol S, Hellgren F, Loré K, Sobkowiak MJ, Gabarrini G, Healy K, Sällberg Chen M, Alici E, Björkström NK, Buggert M, Ljungman P, Sandberg JK, Aleman S, Ljunggren HG
Mol Med 2022 Feb;28(1):20

Respiratory viral infections in otherwise healthy humans with inherited IRF7 deficiency.
Campbell TM, Liu Z, Zhang Q, Moncada-Velez M, Covill LE, Zhang P, Alavi Darazam I, Bastard P, Bizien L, Bucciol G, Lind Enoksson S, Jouanguy E, Karabela ŞN, Khan T, Kendir-Demirkol Y, Arias AA, Mansouri D, Marits P, Marr N, Migeotte I, Moens L, Ozcelik T, Pellier I, Sendel A, Şenoğlu, S, Shahrooei M, Smith CIE, Vandernoot I, Willekens K, Kart Yaşar K, , Bergman P, Abel L, Cobat A, Casanova JL, Meyts I, Bryceson YT
J Exp Med 2022 Jul;219(7):

Salivary IgG to SARS-CoV-2 indicates seroconversion and correlates to serum neutralization in mRNA-vaccinated immunocompromised individuals.
Healy K, Pin E, Chen P, Söderdahl G, Nowak P, Mielke S, Hansson L, Bergman P, Smith CIE, Ljungman P, Valentini D, Blennow O, Österborg A, Gabarrini G, Al-Manei K, Alkharaan H, Sobkowiak MJ, Yousef J, Mravinacova S, Cuapio A, Xu X, Akber M, Loré K, Hellström C, Muschiol S, Bogdanovic G, Buggert M, Ljunggren HG, Hober S, Nilsson P, Aleman S, Sällberg Chen M
Med (N Y) 2022 Feb;3(2):137-153.e3

The association between pre-exposure to glucocorticoids and other immunosuppressant drugs with severe COVID-19 outcomes.
Brodin R, van der Werff SD, Hedberg P, Färnert A, Nauclér P, Bergman P, Requena-Méndez A
Clin Microbiol Infect 2022 Nov;28(11):1477-1485

A flow cytometry-based proliferation assay for clinical evaluation of T-cell memory against SARS-CoV-2.
Lind Enoksson S, Bergman P, Klingström J, Boström F, Da Silva Rodrigues R, Winerdal ME, Marits P
J Immunol Methods 2021 Dec;499():113159

Safety and efficacy of the mRNA BNT162b2 vaccine against SARS-CoV-2 in five groups of immunocompromised patients and healthy controls in a prospective open-label clinical trial.
Bergman P, Blennow O, Hansson L, Mielke S, Nowak P, Chen P, Söderdahl G, Österborg A, Smith CIE, Wullimann D, Vesterbacka J, Lindgren G, Blixt L, Friman G, Wahren-Borgström E, Nordlander A, Gomez AC, Akber M, Valentini D, Norlin AC, Thalme A, Bogdanovic G, Muschiol S, Nilsson P, Hober S, Loré K, Chen MS, Buggert M, Ljunggren HG, Ljungman P, Aleman S,
EBioMedicine 2021 Dec;74():103705

X-linked recessive TLR7 deficiency in ~1% of men under 60 years old with life-threatening COVID-19.
Asano T, Boisson B, Onodi F, Matuozzo D, Moncada-Velez M, Maglorius Renkilaraj MRL, Zhang P, Meertens L, Bolze A, Materna M, Korniotis S, Gervais A, Talouarn E, Bigio B, Seeleuthner Y, Bilguvar K, Zhang Y, Neehus AL, Ogishi M, Pelham SJ, Le Voyer T, Rosain J, Philippot Q, Soler-Palacín P, Colobran R, Martin-Nalda A, Rivière JG, Tandjaoui-Lambiotte Y, Chaïbi K, Shahrooei M, Darazam IA, Olyaei NA, Mansouri D, Hatipoğlu N, Palabiyik F, Ozcelik T, Novelli G, Novelli A, Casari G, Aiuti A, Carrera P, Bondesan S, Barzaghi F, Rovere-Querini P, Tresoldi C, Franco JL, Rojas J, Reyes LF, Bustos IG, Arias AA, Morelle G, Christèle K, Troya J, Planas-Serra L, Schlüter A, Gut M, Pujol A, Allende LM, Rodriguez-Gallego C, Flores C, Cabrera-Marante O, Pleguezuelo DE, de Diego RP, Keles S, Aytekin G, Akcan OM, Bryceson YT, Bergman P, Brodin P, Smole D, Smith CIE, Norlin AC, Campbell TM, Covill LE, Hammarström L, Pan-Hammarström Q, Abolhassani H, Mane S, Marr N, Ata M, Al Ali F, Khan T, Spaan AN, Dalgard CL, Bonfanti P, Biondi A, Tubiana S, Burdet C, Nussbaum R, Kahn-Kirby A, Snow AL, , , , , , , , , , Bustamante J, Puel A, Boisson-Dupuis S, Zhang SY, Béziat V, Lifton RP, Bastard P, Notarangelo LD, Abel L, Su HC, Jouanguy E, Amara A, Soumelis V, Cobat A, Zhang Q, Casanova JL
Sci Immunol 2021 Aug;6(62):

Antimicrobial peptides and Host Directed Therapy

Baricitinib blocks cytokine mediated downregulation of PAD1 in human keratinocytes: a possible molecular link to the effects of JAK-inhibitors in atopic dermatitis.
Padhi A, Rekha RS, Benrejdal L, Grundeken ME, Lourda M, Ehrstöm M, Eyerich K, Páez IT, Johansson EK, Bradley M, Bergman P, Lysell J
J Invest Dermatol 2023 Jan;():

IL-22 Downregulates Peptidylarginine Deiminase-1 in Human Keratinocytes: Adding Another Piece to the IL-22 Puzzle in Epidermal Barrier Formation.
Padhi A, Srivastava A, Ramesh A, Ehrström M, Simon M, Sonkoly E, Eidsmo L, Bergman P, Lysell J
J Invest Dermatol 2022 Feb;142(2):333-342.e6

Low vitamin D is a marker for poor health and increased risk for disease: But causality is still unclear in most cases.
Bergman P
J Intern Med 2022 Oct;():

Vitamin D and Antibiotic Consumption: Another Piece in the Puzzle?
Bergman P
J Infect Dis 2022 Sep;226(6):947-948

Vitamin D Enhances Neutrophil Generation and Function in Zebrafish (Danio rerio).
Liao X, Lan Y, Shao R, Liu J, Liang S, Yin Z, Gudmundsson GH, Bergman P, Wan M
J Innate Immun 2022 ;14(3):229-242

Citrullination Alters the Antibacterial and Anti-Inflammatory Functions of the Host Defense Peptide Canine Cathelicidin K9CATH In Vitro.
Al Adwani S, Padhi A, Karadottir H, Mörman C, Gräslund A, Végvári Á, Johansson J, Rising A, Agerberth B, Bergman P
J Immunol 2021 Aug;207(3):974-984

Immunomodulatory Agents Combat Multidrug-Resistant Tuberculosis by Improving Antimicrobial Immunity.
Rao Muvva J, Ahmed S, Rekha RS, Kalsum S, Groenheit R, Schön T, Agerberth B, Bergman P, Brighenti S
J Infect Dis 2021 Jul;224(2):332-344

'Palliative-D'-Vitamin D Supplementation to Palliative Cancer Patients: A Double Blind, Randomized Placebo-Controlled Multicenter Trial.
Helde Frankling M, Klasson C, Sandberg C, Nordström M, Warnqvist A, Bergqvist J, Bergman P, Björkhem-Bergman L
Cancers (Basel) 2021 Jul;13(15):

The link between vitamin D and COVID-19: distinguishing facts from fiction.
Bergman P
J Intern Med 2021 Jan;289(1):131-133

Vitamin D supplementation to prevent acute respiratory infections: a systematic review and meta-analysis of aggregate data from randomised controlled trials.
Jolliffe DA, Camargo CA, Sluyter JD, Aglipay M, Aloia JF, Ganmaa D, Bergman P, Bischoff-Ferrari HA, Borzutzky A, Damsgaard CT, Dubnov-Raz G, Esposito S, Gilham C, Ginde AA, Golan-Tripto I, Goodall EC, Grant CC, Griffiths CJ, Hibbs AM, Janssens W, Khadilkar AV, Laaksi I, Lee MT, Loeb M, Maguire JL, Majak P, Mauger DT, Manaseki-Holland S, Murdoch DR, Nakashima A, Neale RE, Pham H, Rake C, Rees JR, Rosendahl J, Scragg R, Shah D, Shimizu Y, Simpson-Yap S, Trilok-Kumar G, Urashima M, Martineau AR
Lancet Diabetes Endocrinol 2021 05;9(5):276-292