Host membrane glycosphingolipids and lipid microdomains facilitate Histoplasma capsulatum internalisation by macrophages

Allan J. Guimarães, Mariana Duarte de Cerqueira, Daniel Zamith-Miranda, Pablo H. Lopez, Marcio L. Rodrigues, Bruno Pontes, Nathan B. Viana, Carlos M. DeLeon-Rodriguez, Diego Conrado Pereira Rossi, Arturo Casadevall, Andre M.O. Gomes, Luis R. Martinez, Ronald L. Schnaar, Joshua D. Nosanchuk, Leonardo Nimrichter

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Recognition and internalisation of intracellular pathogens by host cells is a multifactorial process, involving both stable and transient interactions. The plasticity of the host cell plasma membrane is fundamental in this infectious process. Here, the participation of macrophage lipid microdomains during adhesion and internalisation of the fungal pathogen Histoplasma capsulatum (Hc) was investigated. An increase in membrane lateral organisation, which is a characteristic of lipid microdomains, was observed during the first steps of Hc–macrophage interaction. Cholesterol enrichment in macrophage membranes around Hc contact regions and reduced levels of Hc–macrophage association after cholesterol removal also suggested the participation of lipid microdomains during Hc–macrophage interaction. Using optical tweezers to study cell-to-cell interactions, we showed that cholesterol depletion increased the time required for Hc adhesion. Additionally, fungal internalisation was significantly reduced under these conditions. Moreover, macrophages treated with the ceramide-glucosyltransferase inhibitor (P4r) and macrophages with altered ganglioside synthesis (from B4galnt1−/− mice) showed a deficient ability to interact with Hc. Coincubation of oligo-GM1 and treatment with Cholera toxin Subunit B, which recognises the ganglioside GM1, also reduced Hc association. Although purified GM1 did not alter Hc binding, treatment with P4 significantly increased the time required for Hc binding to macrophages. The content of CD18 was displaced from lipid microdomains in B4galnt1−/− macrophages. In addition, macrophages with reduced CD18 expression (CD18low) were associated with Hc at levels similar to wild-type cells. Finally, CD11b and CD18 colocalised with GM1 during Hc–macrophage interaction. Our results indicate that lipid rafts and particularly complex gangliosides that reside in lipid rafts stabilise Hc–macrophage adhesion and mediate efficient internalisation during histoplasmosis.

Original languageEnglish (US)
Article numbere12976
JournalCellular Microbiology
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Histoplasma
Glycosphingolipids
Membrane Lipids
Macrophages
Lipids
Gangliosides
Cholesterol
ceramide glucosyltransferase
Cell Membrane
Optical Tweezers
G(M1) Ganglioside
Histoplasmosis
Membranes
Cholera Toxin
Cell Communication

Keywords

  • glycosphingolipids
  • Histoplasma capsulatum
  • lipid rafts
  • macrophages

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Virology

Cite this

Guimarães, A. J., de Cerqueira, M. D., Zamith-Miranda, D., Lopez, P. H., Rodrigues, M. L., Pontes, B., ... Nimrichter, L. (Accepted/In press). Host membrane glycosphingolipids and lipid microdomains facilitate Histoplasma capsulatum internalisation by macrophages. Cellular Microbiology, [e12976]. https://doi.org/10.1111/cmi.12976

Host membrane glycosphingolipids and lipid microdomains facilitate Histoplasma capsulatum internalisation by macrophages. / Guimarães, Allan J.; de Cerqueira, Mariana Duarte; Zamith-Miranda, Daniel; Lopez, Pablo H.; Rodrigues, Marcio L.; Pontes, Bruno; Viana, Nathan B.; DeLeon-Rodriguez, Carlos M.; Rossi, Diego Conrado Pereira; Casadevall, Arturo; Gomes, Andre M.O.; Martinez, Luis R.; Schnaar, Ronald L.; Nosanchuk, Joshua D.; Nimrichter, Leonardo.

In: Cellular Microbiology, 01.01.2018.

Research output: Contribution to journalArticle

Guimarães, AJ, de Cerqueira, MD, Zamith-Miranda, D, Lopez, PH, Rodrigues, ML, Pontes, B, Viana, NB, DeLeon-Rodriguez, CM, Rossi, DCP, Casadevall, A, Gomes, AMO, Martinez, LR, Schnaar, RL, Nosanchuk, JD & Nimrichter, L 2018, 'Host membrane glycosphingolipids and lipid microdomains facilitate Histoplasma capsulatum internalisation by macrophages', Cellular Microbiology. https://doi.org/10.1111/cmi.12976
Guimarães, Allan J. ; de Cerqueira, Mariana Duarte ; Zamith-Miranda, Daniel ; Lopez, Pablo H. ; Rodrigues, Marcio L. ; Pontes, Bruno ; Viana, Nathan B. ; DeLeon-Rodriguez, Carlos M. ; Rossi, Diego Conrado Pereira ; Casadevall, Arturo ; Gomes, Andre M.O. ; Martinez, Luis R. ; Schnaar, Ronald L. ; Nosanchuk, Joshua D. ; Nimrichter, Leonardo. / Host membrane glycosphingolipids and lipid microdomains facilitate Histoplasma capsulatum internalisation by macrophages. In: Cellular Microbiology. 2018.
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abstract = "Recognition and internalisation of intracellular pathogens by host cells is a multifactorial process, involving both stable and transient interactions. The plasticity of the host cell plasma membrane is fundamental in this infectious process. Here, the participation of macrophage lipid microdomains during adhesion and internalisation of the fungal pathogen Histoplasma capsulatum (Hc) was investigated. An increase in membrane lateral organisation, which is a characteristic of lipid microdomains, was observed during the first steps of Hc–macrophage interaction. Cholesterol enrichment in macrophage membranes around Hc contact regions and reduced levels of Hc–macrophage association after cholesterol removal also suggested the participation of lipid microdomains during Hc–macrophage interaction. Using optical tweezers to study cell-to-cell interactions, we showed that cholesterol depletion increased the time required for Hc adhesion. Additionally, fungal internalisation was significantly reduced under these conditions. Moreover, macrophages treated with the ceramide-glucosyltransferase inhibitor (P4r) and macrophages with altered ganglioside synthesis (from B4galnt1−/− mice) showed a deficient ability to interact with Hc. Coincubation of oligo-GM1 and treatment with Cholera toxin Subunit B, which recognises the ganglioside GM1, also reduced Hc association. Although purified GM1 did not alter Hc binding, treatment with P4 significantly increased the time required for Hc binding to macrophages. The content of CD18 was displaced from lipid microdomains in B4galnt1−/− macrophages. In addition, macrophages with reduced CD18 expression (CD18low) were associated with Hc at levels similar to wild-type cells. Finally, CD11b and CD18 colocalised with GM1 during Hc–macrophage interaction. Our results indicate that lipid rafts and particularly complex gangliosides that reside in lipid rafts stabilise Hc–macrophage adhesion and mediate efficient internalisation during histoplasmosis.",
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AU - Lopez, Pablo H.

AU - Rodrigues, Marcio L.

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AU - Viana, Nathan B.

AU - DeLeon-Rodriguez, Carlos M.

AU - Rossi, Diego Conrado Pereira

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