Riboflavin metabolism variation among clinical isolates of streptococcus pneumoniae results in differential activation of mucosal-Associated invariant T cells

Nadine Hartmann, Curtis McMurtrey, Michelle L. Sorensen, Megan E. Huber, Regina Kurapova, Fadie T. Coleman, Joseph P. Mizgerd, William Hildebrand, Mitchell Kronenberg, David Lewinsohn, Melanie Harriff

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Streptococcus pneumoniae is an important bacterial pathogen that causes a range of noninvasive and invasive diseases. The mechanisms underlying variability in the ability of S. pneumoniae to transition from nasopharyngeal colonization to disease-causing pathogen are not well defined. Mucosal-Associated invariant T (MAIT) cells are prevalent in mucosal tissues such as the airways and are believed to play an important role in the early response to infection with bacterial pathogens. The ability of MAIT cells to recognize and contain infection with S. pneumoniae is not known. In the present study, we analyzed MAIT-cell responses to infection with clinical isolates of S. pneumoniae serotype 19A, a serotype linked to invasive pneumococcal disease. We found that although MAIT cells were capable of responding to human dendritic and airway epithelial cells infected with S. pneumoniae, the magnitude of response to different serotype 19A isolates was determined by genetic differences in the expression of the riboflavin biosynthesis pathway. MAIT-cell release of cytokines correlated with differences in the ability of MAIT cells to respond to and control S. pneumoniae in vitro and in vivo in a mouse challenge model. Together, these results demonstrate first that there are genetic differences in riboflavin metabolism among clinical isolates of the same serotype and second that these likely determine MAIT-cell function in response to infection with S. pneumoniae. These differences are critical when considering the role that MAIT cells play in early responses to pneumococcal infection and determining whether invasive disease will develop.

Original languageEnglish (US)
Pages (from-to)767-776
Number of pages10
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume58
Issue number6
DOIs
StatePublished - Jun 1 2018

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T-cells
Riboflavin
Streptococcus pneumoniae
Metabolism
Chemical activation
Pneumococcal Infections
Pathogens
Mucosal-Associated Invariant T Cells
Biosynthesis
Bacterial Infections
Mucous Membrane
Epithelial Cells
Cytokines
Serogroup
Infection

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

Cite this

Riboflavin metabolism variation among clinical isolates of streptococcus pneumoniae results in differential activation of mucosal-Associated invariant T cells. / Hartmann, Nadine; McMurtrey, Curtis; Sorensen, Michelle L.; Huber, Megan E.; Kurapova, Regina; Coleman, Fadie T.; Mizgerd, Joseph P.; Hildebrand, William; Kronenberg, Mitchell; Lewinsohn, David; Harriff, Melanie.

In: American Journal of Respiratory Cell and Molecular Biology, Vol. 58, No. 6, 01.06.2018, p. 767-776.

Research output: Contribution to journalArticle

Hartmann, Nadine ; McMurtrey, Curtis ; Sorensen, Michelle L. ; Huber, Megan E. ; Kurapova, Regina ; Coleman, Fadie T. ; Mizgerd, Joseph P. ; Hildebrand, William ; Kronenberg, Mitchell ; Lewinsohn, David ; Harriff, Melanie. / Riboflavin metabolism variation among clinical isolates of streptococcus pneumoniae results in differential activation of mucosal-Associated invariant T cells. In: American Journal of Respiratory Cell and Molecular Biology. 2018 ; Vol. 58, No. 6. pp. 767-776.
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