Immunology and aerobiology of mycobacteria

We study Dendritic cells and the immune response to mycobacteria. We are also interested in the We are also interested in the aerosol transmission of Mycobacterium tuberculosis and are developing technology to collect and study mycobacteria from aerosols.

 

Research focus

High-resolution confocal microscopy
High-resolution confocal microscopy showing apposition of IL-12p40-producing dendritic cells (green) with T cells (red) in lymph node containing BCG (white). Photo: Antonio Rothfuchs.

Dendritic cell responses to mycobacteria

Dendritic cells sense invading microbes at the site of infection and respond by internalizing the microbe and moving via lymphatic vessels to the regional, draining lymph node, where they activate naïve T cells. This process is incompletely understood for both M. tuberculosis and M. bovis Bacille Calmette-Guérin (BCG), the live tuberculosis vaccine. We are interested in the activation and response capacity of Dendritic cells to BCG, including the mechanisms by which migratory Dendritic cells mobilize to the lymph node in response to BCG, their ability to transport BCG to the lymph node, and to trigger the activation of protective CD4+ T cells. Understanding the above will help rationalize strategies in tuberculosis control by harnessing Dendritic cells for clinical benefit and for improving BCG as well as other vaccines of low-to-modest efficacy. 

THOR electrostatic air sampler.

An air sampler for M. tuberculosis

Tuberculosis spreads by inhalation of aerosols, generated during coughing that contain M. tuberculosis. Air sampling technology could play an important role in controlling tuberculosis transmission by enabling the detection of airborne M. tuberculosis, identifying hotspots of transmission and cases of active tuberculosis. Tools that are easy-to-use and scalable in low-income, high-burden countries are however lacking. With this in mind we have developed a compact and affordable electrostatic air sampler that can be used together with nucleic acid amplification tests to detect M. tuberculosis in aerosols. The performance of this new device to detect aerosolized M. tuberculosis is being investigated in collaboration with the Department of Global Public Health, Karolinska Institutet, clinical and pre-clinical partners in Sweden, South Africa and Moçambique. The device is also being used to investigate the presence of SARS-CoV-2 in air.

Aerosol chamber
Test chamber tailored for aerosol dispersal experiments with mycobacteria and other agents. Photo: Antonio Gigliotti Rothfuchs

Impact of aerosol transport on mycobacterial survival and infectivity 

Despite progress on the infection biology of M. tuberculosis, little is known about the pathogen in its transmissible, aerosol form and the consequences of aerosol transport on mycobacterial survival and infectivity. Using a unique aerosol chamber, we have recently developed a setup to collect aerosolized mycobacteria, to study their survival and gene expression in aerosols, and infectivity in macrophages, the target cell for mycobacterial replication. This platform has been tailored for BSL-3 containment work with aerosolized M. tuberculosis and other risk group 3 airborne pathogens such as SARS-CoV-2.

These aerobiology studies will contribute important new information on host-mycobacteria interactions, M. tuberculosis transmission and the implementation of transmission-blocking strategies in tuberculosis control.

Selected publications

Massive and rapid COVID-19 testing is feasible by extraction-free SARS-CoV-2 RT-PCR.
Smyrlaki I, Ekman M, Lentini A, Rufino de Sousa N, Papanicolaou N, Vondracek M, et al
Nat Commun 2020 09;11(1):4812

Operative and Technical Modifications to the Coriolis® µ Air Sampler That Improve Sample Recovery and Biosafety During Microbiological Air Sampling.
Rufino de Sousa N, Shen L, Silcott D, Call CJ, Rothfuchs AG
Ann Work Expo Health 2020 May;():

A fieldable electrostatic air sampler enabling tuberculosis detection in bioaerosols.
Rufino de Sousa N, Sandström N, Shen L, Håkansson K, Vezozzo R, Udekwu KI, et al
Tuberculosis (Edinb) 2020 Jan;120():101896

Atrophy of skin-draining lymph nodes predisposes for impaired immune responses to secondary infection in mice with chronic intestinal nematode infection.
Feng X, Classon C, Terán G, Yang Y, Li L, Chan S, et al
PLoS Pathog. 2018 05;14(5):e1007008

Immunogenicity is preferentially induced in sparse dendritic cell cultures.
Nasi A, Bollampalli VP, Sun M, Chen Y, Amu S, Nylén S, et al
Sci Rep 2017 03;7():43989

A CFSE-based Assay to Study the Migration of Murine Skin Dendritic Cells into Draining Lymph Nodes During Infection with Mycobacterium bovis Bacille Calmette-Guérin.
Bollampalli VP, Nylén S, Rothfuchs AG
J Vis Exp 2016 10;(116):

BCG Skin Infection Triggers IL-1R-MyD88-Dependent Migration of EpCAMlow CD11bhigh Skin Dendritic cells to Draining Lymph Node During CD4+ T-Cell Priming.
Bollampalli VP, Harumi Yamashiro L, Feng X, Bierschenk D, Gao Y, Blom H, et al
PLoS Pathog. 2015 Oct;11(10):e1005206

Chronic Gastrointestinal Nematode Infection Mutes Immune Responses to Mycobacterial Infection Distal to the Gut.
Obieglo K, Feng X, Bollampalli VP, Dellacasa-Lindberg I, Classon C, Österblad M, et al
J. Immunol. 2016 Mar;196(5):2262-71

Nucleotide-binding oligomerization domain-2 (NOD2) regulates type-1 cytokine responses to Mycobacterium avium but is not required for host control of infection.
Carvalho NB, Oliveira FS, Marinho FA, de Almeida LA, Fahel JS, Báfica A, et al
Microbes Infect. 2015 May;17(5):337-44

IL-10 limits parasite burden and protects against fatal myocarditis in a mouse model of Trypanosoma cruzi infection.
Roffê E, Rothfuchs AG, Santiago HC, Marino AP, Ribeiro-Gomes FL, Eckhaus M, et al
J. Immunol. 2012 Jan;188(2):649-60

Intravital imaging reveals limited antigen presentation and T cell effector function in mycobacterial granulomas.
Egen JG, Rothfuchs AG, Feng CG, Horwitz MA, Sher A, Germain RN
Immunity 2011 May;34(5):807-19

Intranasal Poly-IC treatment exacerbates tuberculosis in mice through the pulmonary recruitment of a pathogen-permissive monocyte/macrophage population.
Antonelli LR, Gigliotti Rothfuchs A, Gonçalves R, Roffê E, Cheever AW, Bafica A, et al
J. Clin. Invest. 2010 May;120(5):1674-82

In situ IL-12/23p40 production during mycobacterial infection is sustained by CD11bhigh dendritic cells localized in tissue sites distinct from those harboring bacilli.
Rothfuchs AG, Egen JG, Feng CG, Antonelli LR, Bafica A, Winter N, et al
J. Immunol. 2009 Jun;182(11):6915-25

Macrophage and T cell dynamics during the development and disintegration of mycobacterial granulomas.
Egen JG, Rothfuchs AG, Feng CG, Winter N, Sher A, Germain RN
Immunity 2008 Feb;28(2):271-84

Dectin-1 interaction with Mycobacterium tuberculosis leads to enhanced IL-12p40 production by splenic dendritic cells.
Rothfuchs AG, Bafica A, Feng CG, Egen JG, Williams DL, Brown GD, et al
J. Immunol. 2007 Sep;179(6):3463-71

Group members

Antonio Gigliotti Rothfuchs

Principal researcher
08-524 852 52

Nuno Ramos Rufino de Sousa

Laboratory technician

Veronika Krmeska

PhD student

Jay Achar

PhD Student

Duncan Njenda

Laboratory engineer

Marjo-Riitta Puumalainen

Project manager

Former group members

  • Lei Shen, postdoc, 2017-2019. Now Shanghai Pulmonary Hospital, China
  • Juliana Aggio, visiting PhD student from ICC/Fiocruz Brazil, 2018-2019. Now postdoc Fiocruz.
  • Pryscilla Wowk, postdoc/visiting researcher from ICC/Fiocruz Brazil, 2017-2018
  • Niklas Sandström, postdoc, 2015-2017. Now SciLifeLab, Stockholm
  • Vishnu Priya Bollampalli, PhD student. Defended in 2017. Now Cepheid, Stockholm.
  • Jintao Guo, postdoc, 2016-2017. Now Legend Biotech, Nanjing, China.
  • Sara Fernandez Leon, research assistant, 2016-2017
  • Livia Yamashiro, visiting PhD student from UFSC Brazil, 2014. Now Arcus Biosciences, USA.

Collaboration with companies

In addition to academic collaborations we also work with companies and research institutes in different projects related to tuberculosis, aerobiology or infection control. Some of our current and previous private sector partnerships include:

  • Cepheid, USA
  • Semair Diagnostics, Sweden
  • Sarepta Therapeutics, USA
  • S3I, USA
  • Zeteo Tech, USA

Research Funding

Our research has received funding from various sources over the years. We acknowledge the generous support from the following bodies that have funded research in the group or enabled researchers to come and work with us:

  • Bill and Melinda Gates Foundation, USA
  • CAPES, Brazil
  • China Scholarship Council CSC
  • European Research Council
  • Karolinska Institutet
  • Karolinska Innovations AB
  • SciLifeLab
  • STINT
  • Swedish Research Council VR
  • Swedish Society for Medicine
  • Åke Wiberg Stiftelse