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Mycobacterium avium avium and Mycobacterium avium hominissuis give different cytokine responses after in vitro stimulation of human blood mononuclear cells
Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
Department of Infectious Medicine, Institute of Biomedicine, University of Gothenburg, Sweden.
Linköping University, Department of Medical and Health Sciences, Clinical Physiology. Linköping University, Faculty of Health Sciences.
Infectious Diseases, Department of Medical Sciences, Uppsala University and Academic Hospital, Uppsala, Sweden.
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2012 (English)In: PLoS ONE, ISSN 1932-6203, Vol. 7, no 4, e34391- p.Article in journal (Refereed) Published
Abstract [en]

Background: Mycobacterium avium is the principal etiologic agent of non-tuberculous lymphadenitis in children. It is also a known pathogen for birds and other animals. Molecular epidemiologic evidence indicates that humans and animals are infected with different M. avium subspecies, namely, M. avium subsp. avium and M. avium subsp. hominissuis, respectively.

Aim: To investigate the effect on the human immune system of 10 isolates of M. avium subsp. avium mainly isolated from animals and of 11 isolates of M. avium subsp. hominissuis isolated from children with lymphadenitis.

Method: Peripheral blood mononuclear cells (PBMC) from six healthy blood donors were stimulated in vitro with the inactivated mycobacteria followed by quantification of IL-10, IL-12p70, TNF, IFN-γ and IL-17 in supernatants by multiplex bead array analysis (Luminex).

Results: M. avium subsp. hominissuis induced significantly more IL-10 and significantly less IL-12p70, TNF, IFN-γ and IL-17 compared to M. avium subsp. avium. All strains induced high levels of IL-17, but very little IL-12.

Conclusion: The lower T helper (Th) 1 and Th17 responses induced by M. avium subsp. hominissuis compared to M. avium subsp. avium after in vitro stimulation of PBMC might contribute to its higher pathogenicity in humans.

Place, publisher, year, edition, pages
PloS , 2012. Vol. 7, no 4, e34391- p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-53785DOI: 10.1371/journal.pone.0034391ISI: 000305297500026OAI: diva2:291872
Available from: 2010-02-03 Created: 2010-02-03 Last updated: 2013-11-07
In thesis
1. Mycobacterium avium infections in children
Open this publication in new window or tab >>Mycobacterium avium infections in children
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Mycobacterium avium belongs to a group of over 130 species of non-tuberculous mycobacteria (NTM) or environmental mycobacteria. The subspecies Mycobacterium avium avium was originally described as the causative agent of bird tuberculosis, but was later found to cause disease also in humans. Small children display a special form of infection that is seldom detected in other age groups. It manifests as a chronic lymphadenitis usually in the head and neck region. The incidence rate is approximately 1-5/100,000 children/year. However, exposure to this bacterium is high as judged by sensitin skin test studies. Even if a lot of persons are infected with M. avium, a majority of them do not develop disease and the bacterium is therefore considered to be of low virulence, causing disease mainly in immunocompromised persons. Children with M. avium lymphadenitis, however, usually do not have any known deficiencies in the immune system.

This thesis elucidates why small children are prone to develop disease by M. avium. Investigation of a possible zoonotic spread of this bacterium to children involved analysis and comparison of different strains isolated from birds and other animals and from children, using the restriction fragment length polymorphism (RFLP) method on insertion sequence IS1245, resulting in the finding that the children were infected exclusively with the new proposed subspecies M. avium hominissuis. Animals in general and birds in particular were infected with the subspecies M. avium avium (using the more narrow definition). Moreover, when investigating the immunological response of human peripheral blood mononuclear cells (PBMCs) to stimulation with M. avium hominissuis and M. avium avium, respectively, it was found that the former subspecies induced lower IFN-γ and IL-17 than the latter, but higher levels of Il-10, which might contribute to explain the higher pathogenicity of M. avium hominissuis in humans.

Through studies of the geographical distribution of cases of M. avium infection in children in Sweden and the seasonal variation of the disease, a fluctuation of the incidence over the year was detected, with higher numbers of cases in the autumn months and lower numbers in the late spring. There was a higher incidence rate in children living close to water than in those living in the inland or in the urban areas. Therefore, outdoor natural water is the most probable source of infection in children with M. avium lymphadenitis. Through a descriptive clinical retrospective study, complete surgical removal of the affected lymph node was found to lead to better results than treatment by incision and drainage of abscess or expectation only.

Finally there might be several explanations as to why an individual develops disease after infection with M. avium, such as, exposure, bacterial virulence factors or possible specific deficiencies of the immune system of the host or a combination of these factors. Which are the more important factors regarding children with M. avium lymphadenitis is still an open question.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2009. 76 p.
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1130
National Category
Medical and Health Sciences
urn:nbn:se:liu:diva-53786 (URN)978-91-7393-623-1 (ISBN)
Public defence
2009-05-29, Fullriggaren, Kalmar Högskola, Kalmar, 13:00 (English)
Available from: 2010-02-03 Created: 2010-02-03 Last updated: 2010-02-03Bibliographically approved

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