Elemental ingredients in the macrophage cocktail

Role of zip8 in host response to Mycobacterium tuberculosis

Charlie J. Pyle, Abul K. Azad, Audrey C. Papp, Wolfgang Sadee, Daren L Knoell, Larry S. Schlesinger

Research output: Contribution to journalReview article

6 Citations (Scopus)

Abstract

Tuberculosis (TB) is a global epidemic caused by the infection of human macrophages with the world’s most deadly single bacterial pathogen, Mycobacterium tuberculosis (M.tb). M.tb resides in a phagosomal niche within macrophages, where trace element concentrations impact the immune response, bacterial metal metabolism, and bacterial survival. The manipulation of micronutrients is a critical mechanism of host defense against infection. In particular, the human zinc transporter Zrt-/Irt-like protein 8 (ZIP8), one of 14 ZIP family members, is important in the flux of divalent cations, including zinc, into the cytoplasm of macrophages. It also has been observed to exist on the membrane of cellular organelles, where it can serve as an efflux pump that transports zinc into the cytosol. ZIP8 is highly inducible in response to M.tb infection of macrophages, and we have observed its localization to the M.tb phagosome. The expression, localization, and function of ZIP8 and other divalent cation transporters within macrophages have important implications for TB prevention and dissemination and warrant further study. In particular, given the importance of zinc as an essential nutrient required for humans and M.tb, it is not yet clear whether ZIP-guided zinc transport serves as a host protective factor or, rather, is targeted by M.tb to enable its phagosomal survival.

Original languageEnglish (US)
Article number2375
JournalInternational Journal of Molecular Sciences
Volume18
Issue number11
DOIs
StatePublished - Nov 9 2017

Fingerprint

tuberculosis
macrophages
Macrophages
Mycobacterium tuberculosis
ingredients
Zinc
zinc
Divalent Cations
Proteins
infectious diseases
transporter
Positive ions
Tuberculosis
proteins
Micronutrients
Trace Elements
Pathogens
Phagosomes
Mycobacterium Infections
Trace elements

Keywords

  • Innate immunity
  • Lung
  • Macrophage
  • Tuberculosis
  • Zinc
  • Zinc transporter

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

Elemental ingredients in the macrophage cocktail : Role of zip8 in host response to Mycobacterium tuberculosis. / Pyle, Charlie J.; Azad, Abul K.; Papp, Audrey C.; Sadee, Wolfgang; Knoell, Daren L; Schlesinger, Larry S.

In: International Journal of Molecular Sciences, Vol. 18, No. 11, 2375, 09.11.2017.

Research output: Contribution to journalReview article

Pyle, Charlie J. ; Azad, Abul K. ; Papp, Audrey C. ; Sadee, Wolfgang ; Knoell, Daren L ; Schlesinger, Larry S. / Elemental ingredients in the macrophage cocktail : Role of zip8 in host response to Mycobacterium tuberculosis. In: International Journal of Molecular Sciences. 2017 ; Vol. 18, No. 11.
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