Research group Bergman/Agerberth - The AMP-group

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We study the role of antimicrobial peptides (AMPs) in human immunity. The current focus is on respiratory tract infections, including tuberculosis, and the intestinal barrier function, especially in the context of HIV. 

AMPs are expressed in mucosal tissues and by immune-cells. They constitute important effector molecules in the innate immune system. AMPs have potent antimicrobial activity against bacteria, viruses and fungi. In addition, AMPs function as "alarmins", i.e they activate and recruit cells from the adaptive immune system to the site of infection. AMP expression is tightly regulated but recent knowledge has revealed that substances such as vitamin D and phenylbutyrate (PBA) can induce AMP-expression in mucosal tissues and immune-cells.

Our aim is to translate basic findings on AMP-expression and regulation into clinical practice. In particular we work with a concept named “Host Directed Therapy”, which involves activation or induction of antimicrobial peptides by using small molecular compounds, such as vitamin D and Phenylbutyrate (PBA). Our aim is to identify novel and more potent inducers of AMP expression. In addition, we work with mechanistic studies on human tissues and cells but also perform clinical trials, where inducers of AMP-expression are investigated in humans.

Recently, we showed that vitamin D and PBA could activate autophagy in human macrophages, a process that is necessary to inhibit intracellular growth of Mycobacterium tuberculosis (Mtb). We could further show that autophagy and the control of Mtb-growth was depending on the human antimicrobial peptide LL-37.

We now plan to continue along these lines and to dissect the mechanisms in great detail. In addition, several clinical trials with vitamin D and/or PBA are ongoing or in the planning phase.

Research group leaders

Senior lecturer/clinical

Peter Bergman

Organizational unit: Division of Clinical Microbiology
E-mail: Peter.Bergman@ki.se

Professor, senior

Birgitta Agerberth

Organizational unit: Division of Clinical Microbiology
E-mail: Birgitta.Agerberth@ki.se

Our research in Media

The research on vitamin D/PBA and tuberculosis was recently presented on the KI website.

Previously, we have shown that patients with immunodeficiency can reduce their infectious burden and antibiotic consumption by vitamin D supplementation. Read article on the KI website here.

In another project, we have – together with a French group – shown that the antimicrobial peptide CRAMP can protect against type I diabetes in the mouse. Read lint the article published in Immunity.

Ongoing projects

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

  • Phenylbutyrate and Vitamin D as host directed therapy in tuberculosis – experimental and clinical studies in Bangladesh and Ethiopia
  • A cellular infection model to evaluate novel host directed therapy with implications for multi drug resistant bacteria
  • Studies of the expression and regulation of antimicrobial peptides – focus on transcription factors
  • The role of vitamin D in HIV – focus on the intestinal barrier function
  • Vitamin D and respiratory tract infections – experimental and clinical studies
  • Diagnostic and pathophysiological aspects of sepsis-causing bacteria

Group members

Professor, senior

Birgitta Agerberth

Organizational unit: Division of Clinical Microbiology
E-mail: Birgitta.Agerberth@ki.se

Postdoc

Sultan Ahmed

Organizational unit: Division of Clinical Microbiology
E-mail: sultan.ahmed@ki.se

Graduate Student

Salma Al Adwani

Organizational unit: Department of Laboratory Medicine (LABMED), H5
E-mail: salma.al.adwani@ki.se

Senior lecturer/clinical

Peter Bergman

Organizational unit: Division of Clinical Microbiology
E-mail: Peter.Bergman@ki.se

Senior researcher

Linda Björkhem-Bergman

Organizational unit: Division of Clinical Microbiology
E-mail: Linda.Bjorkhem-Bergman@ki.se

Associated

Maarten Coorens

Organizational unit: Division of Clinical Microbiology
E-mail: maarten.coorens@ki.se

Graduate Student

Harpa Karadottir

E-mail: harpa.karadottir@ki.se

Graduate Student

Catharina Missailidis

Organizational unit: Division of Clinical Microbiology
E-mail: catharina.missailidis@ki.se

PhD student

Rokeya Sultana Rekha

Organizational unit: Division of Clinical Microbiology
E-mail: rokeya.sultana.rekha@ki.se

Laboratory coordinator

Min Wan

Organizational unit: Division of Clinical Microbiology
E-mail: Min.Wan@ki.se

Research techniques

  • Cell-culture 
  • Immunohistochemistry
  • Expression analysis byq RT-PCR and Western blot
  • Microbiological work with bacteria
  • Biochemical purification of antimicrobial peptides using HPLC and mass-spectrometry
  • ChIP-assays
  • CRISPR/Cas9-gene editing

External funding

Swedish Research Council, Heart-Lung Foundation, Swedish Cancer Foundation, Stockholm County Council, Karolinska Institutet, Swedish Foundation for Strategic Research (SSF), the Groschinsky Foundation, the Scandinavian Society for Antimicrobial Research, Swedish Society for Physicians

Selected publications

Assays for Identifying Inducers of the Antimicrobial Peptide LL-37.
Nylén F, Bergman P, Gudmundsson G, Agerberth B
Methods Mol. Biol. 2017 ;1548():271-281

Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data.
Martineau A, Jolliffe D, Hooper R, Greenberg L, Aloia J, Bergman P, et al
BMJ 2017 Feb;356():i6583

Potent Inducers of Endogenous Antimicrobial Peptides for Host Directed Therapy of Infections.
Ottosson H, Nylén F, Sarker P, Miraglia E, Bergman P, Gudmundsson G, et al
Sci Rep 2016 Nov;6():36692

Entinostat up-regulates the CAMP gene encoding LL-37 via activation of STAT3 and HIF-1α transcription factors.
Miraglia E, Nylén F, Johansson K, Arnér E, Cebula M, Farmand S, et al
Sci Rep 2016 Sep;6():33274

Cathelicidins positively regulate pancreatic β-cell functions.
Sun J, Xu M, Ortsäter H, Lundeberg E, Juntti-Berggren L, Chen Y, et al
FASEB J. 2016 Feb;30(2):884-94

Significant Effects of Oral Phenylbutyrate and Vitamin D3 Adjunctive Therapy in Pulmonary Tuberculosis: A Randomized Controlled Trial.
Mily A, Rekha R, Kamal S, Arifuzzaman A, Rahim Z, Khan L, et al
PLoS ONE 2015 ;10(9):e0138340

Pancreatic β-Cells Limit Autoimmune Diabetes via an Immunoregulatory Antimicrobial Peptide Expressed under the Influence of the Gut Microbiota.
Sun J, Furio L, Mecheri R, van der Does A, Lundeberg E, Saveanu L, et al
Immunity 2015 Aug;43(2):304-17

Phenylbutyrate induces LL-37-dependent autophagy and intracellular killing of Mycobacterium tuberculosis in human macrophages.
Rekha R, Rao Muvva S, Wan M, Raqib R, Bergman P, Brighenti S, et al
Autophagy 2015 ;11(9):1688-99

Low vitamin D levels are associated with higher opioid dose in palliative cancer patients--results from an observational study in Sweden.
Bergman P, Sperneder S, Höijer J, Bergqvist J, Björkhem-Bergman L
PLoS ONE 2015 ;10(5):e0128223

Narcolepsy patients have antibodies that stain distinct cell populations in rat brain and influence sleep patterns.
Bergman P, Adori C, Vas S, Kai-Larsen Y, Sarkanen T, Cederlund A, et al
Proc. Natl. Acad. Sci. U.S.A. 2014 Sep;111(35):E3735-44

Vitamin D3 supplementation in patients with frequent respiratory tract infections: a randomised and double-blind intervention study.
Bergman P, Norlin A, Hansen S, Rekha R, Agerberth B, Björkhem-Bergman L, et al
BMJ Open 2012 ;2(6):

Infectious Disease MedicineInflammationMicrobiology