All-Trans Retinoic Acid in Combination with Primaquine Clears Pneumocystis Infection

Guang Sheng Lei, Chen Zhang, Shoujin Shao, Hsin Wei Jung, Pamela J. Durant, Chao-Hung Lee

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Pneumocystis pneumonia (PcP) develops in immunocompromised patients. Alveolar macrophages play a key role in the recognition, phagocytosis, and degradation of Pneumocystis, but their number is decreased in PcP. Our study of various inflammatory components during PcP found that myeloid-derived suppressor cells (MDSCs) accumulate in the lungs of mice and rats with Pneumocystis pneumonia (PcP). We hypothesized that treatment with all-trans retinoic acid (ATRA), a metabolite of vitamin A, may effectively control Pneumocystis (Pc) infection by inducing MDSCs to differentiate to AMs. In rodent models of PcP, we found that 5 weeks of ATRA treatment reduced the number of MDSCs in the lungs and increased the number of AMs which cleared Pc infection. We also found that ATRA in combination with primaquine was as effective as the combination of trimethoprim and sulfamethaxazole for treatment of PcP and completely eliminated MDSCs and Pc organisms in the lungs in two weeks. No relapse of PcP was seen after three weeks of the ATRA-primaquine combination treatment. Prolonged survival of Pc-infected animals was also achieved by this regimen. This is the very first successful development of a therapeutic regimen for PcP that combines an immune modulator with an antibiotic, enabling the hosts to effectively defend the infection. Results of our study may serve as a model for development of novel therapies for other infections with MDSC accumulation.

Original languageEnglish
Article numbere53479
JournalPLoS One
Volume8
Issue number1
DOIs
StatePublished - Jan 4 2013

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Pneumocystis Infections
Primaquine
Pneumocystis
Pneumocystis Pneumonia
retinoic acid
Tretinoin
pneumonia
suppressor cells
infection
Trimethoprim
Metabolites
Vitamin A
Lung
Modulators
Rats
Animals
lungs
Anti-Bacterial Agents
Degradation
Alveolar Macrophages

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

All-Trans Retinoic Acid in Combination with Primaquine Clears Pneumocystis Infection. / Lei, Guang Sheng; Zhang, Chen; Shao, Shoujin; Jung, Hsin Wei; Durant, Pamela J.; Lee, Chao-Hung.

In: PLoS One, Vol. 8, No. 1, e53479, 04.01.2013.

Research output: Contribution to journalArticle

Lei, Guang Sheng ; Zhang, Chen ; Shao, Shoujin ; Jung, Hsin Wei ; Durant, Pamela J. ; Lee, Chao-Hung. / All-Trans Retinoic Acid in Combination with Primaquine Clears Pneumocystis Infection. In: PLoS One. 2013 ; Vol. 8, No. 1.
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