Macrophage autophagy in immunity to Cryptococcus neoformans and Candida albicans

André Moraes Nicola, Patrícia Albuquerque, Luis R. Martinez, Rafael Antonio Dal-Rosso, Carolyn Saylor, Magdia De Jesus, Joshua D. Nosanchuk, Arturo Casadevall

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

Autophagy is used by eukaryotes in bulk cellular material recycling and in immunity to intracellular pathogens. We evaluated the role of macrophage autophagy in the response to Cryptococcus neoformans and Candida albicans, two important opportunistic fungal pathogens. The autophagosome marker LC3 (microtubule-associated protein 1 light chain 3 alpha) was present in most macrophage vacuoles containing C. albicans. In contrast, LC3 was found in only a few vacuoles containing C. neoformans previously opsonized with antibody but never after complement-mediated phagocytosis. Disruption of host autophagy in vitro by RNA interference against ATG5 (autophagy-related 5) decreased the phagocytosis of C. albicans and the fungistatic activity of J774.16 macrophage-like cells against both fungi, independent of the opsonin used. ATG5-knockout bone marrow-derived macrophages (BMMs) also had decreased fungistatic activity against C. neoformans when activated. In contrast, nonactivated ATG5-knockout BMMs actually restricted C. neoformans growth more efficiently, suggesting that macrophage autophagy plays different roles against C. neoformans, depending on the macrophage type and activation. Interference with autophagy in J774.16 cells also decreased nonlytic exocytosis of C. neoformans, increased interleukin-6 secretion, and decreased gamma interferon-induced protein 10 secretion. Mice with a conditionally knocked out ATG5 gene in myeloid cells showed increased susceptibility to intravenous C. albicans infection. In contrast, these mice manifested no increased susceptibility to C. neoformans, as measured by survival, but had fewer alternatively activated macrophages and less inflammation in the lungs after intratracheal infection than control mice. These results demonstrate the complex roles of macrophage autophagy in restricting intracellular parasitism by fungi and reveal connections with nonlytic exocytosis, humoral immunity, and cytokine signaling.

Original languageEnglish (US)
Pages (from-to)3065-3076
Number of pages12
JournalInfection and Immunity
Volume80
Issue number9
DOIs
StatePublished - Sep 2012

Fingerprint

Cryptococcus neoformans
Autophagy
Candida albicans
Immunity
Macrophages
Exocytosis
Vacuoles
Phagocytosis
Fungi
Opsonin Proteins
Microtubule-Associated Proteins
Macrophage Activation
Recycling
Myeloid Cells
Humoral Immunity
Infection Control
RNA Interference
Eukaryota
Interferon-gamma
Interleukin-6

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Parasitology
  • Infectious Diseases

Cite this

Nicola, A. M., Albuquerque, P., Martinez, L. R., Dal-Rosso, R. A., Saylor, C., De Jesus, M., ... Casadevall, A. (2012). Macrophage autophagy in immunity to Cryptococcus neoformans and Candida albicans. Infection and Immunity, 80(9), 3065-3076. https://doi.org/10.1128/IAI.00358_12

Macrophage autophagy in immunity to Cryptococcus neoformans and Candida albicans. / Nicola, André Moraes; Albuquerque, Patrícia; Martinez, Luis R.; Dal-Rosso, Rafael Antonio; Saylor, Carolyn; De Jesus, Magdia; Nosanchuk, Joshua D.; Casadevall, Arturo.

In: Infection and Immunity, Vol. 80, No. 9, 09.2012, p. 3065-3076.

Research output: Contribution to journalArticle

Nicola, AM, Albuquerque, P, Martinez, LR, Dal-Rosso, RA, Saylor, C, De Jesus, M, Nosanchuk, JD & Casadevall, A 2012, 'Macrophage autophagy in immunity to Cryptococcus neoformans and Candida albicans', Infection and Immunity, vol. 80, no. 9, pp. 3065-3076. https://doi.org/10.1128/IAI.00358_12
Nicola AM, Albuquerque P, Martinez LR, Dal-Rosso RA, Saylor C, De Jesus M et al. Macrophage autophagy in immunity to Cryptococcus neoformans and Candida albicans. Infection and Immunity. 2012 Sep;80(9):3065-3076. https://doi.org/10.1128/IAI.00358_12
Nicola, André Moraes ; Albuquerque, Patrícia ; Martinez, Luis R. ; Dal-Rosso, Rafael Antonio ; Saylor, Carolyn ; De Jesus, Magdia ; Nosanchuk, Joshua D. ; Casadevall, Arturo. / Macrophage autophagy in immunity to Cryptococcus neoformans and Candida albicans. In: Infection and Immunity. 2012 ; Vol. 80, No. 9. pp. 3065-3076.
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