Research group Bergman/Agerberth - The AMP-group
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 leader Peter Bergman
Our research in Media
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.
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
- Expression analysis byq RT-PCR and Western blot
- Microbiological work with bacteria
- Biochemical purification of antimicrobial peptides using HPLC and mass-spectrometry
- CRISPR/Cas9-gene editing
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
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
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 Feb;():
The vitamin D analogue calcipotriol promotes an anti-tumorigenic phenotype of human pancreatic CAFs but reduces T cell mediated immunity.
Gorchs L, Ahmed S, Mayer C, Knauf A, Fernández Moro C, Svensson M, Heuchel R, Rangelova E, Bergman P, Kaipe H
Sci Rep 2020 10;10(1):17444
Mannose receptor-derived peptides neutralize pore-forming toxins and reduce inflammation and development of pneumococcal disease.
Subramanian K, Iovino F, Tsikourkitoudi V, Merkl P, Ahmed S, Berry SB, Aschtgen MS, Svensson M, Bergman P, Sotiriou GA, Henriques-Normark B
EMBO Mol Med 2020 11;12(11):e12695
The link between vitamin D and COVID-19: distinguishing facts from fiction.
J Intern Med 2021 01;289(1):131-133
Host Directed Therapy Against Infection by Boosting Innate Immunity.
Bergman P, Raqib R, Rekha RS, Agerberth B, Gudmundsson GH
Front Immunol 2020 ;11():1209
Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data.
Martineau AR, Jolliffe DA, Hooper RL, Greenberg L, Aloia JF, Bergman P, et al
BMJ 2017 Feb;356():i6583
Cathelicidins positively regulate pancreatic β-cell functions.
Sun J, Xu M, Ortsäter H, Lundeberg E, Juntti-Berggren L, Chen YQ, 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 RS, Kamal SM, Arifuzzaman AS, 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 AM, 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 RS, Rao Muvva SS, Wan M, Raqib R, Bergman P, Brighenti S, et al
Autophagy 2015 ;11(9):1688-99
Vitamin D3 supplementation in patients with frequent respiratory tract infections: a randomised and double-blind intervention study.
Bergman P, Norlin AC, Hansen S, Rekha RS, Agerberth B, Björkhem-Bergman L, et al
BMJ Open 2012 ;2(6):