Molecular mechanism to recruit galectin-3 into multivesicular bodies for polarized exosomal secretion

Bänfer, Sebastian; Schneider, Dominik; Dewes, Jenny; Strauss, Maximilian T.; Freibert, Sven‐Andreas; Heimerl, Thomas; Maier, Uwe G.; Elsässer, Hans–Peter; Jungmann, Ralf; Jacob, Ralf

doi:10.1073/pnas.1718921115

Cited by 102 publications

(93 citation statements)

References 87 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Hsp90 is abundantly present in the serum of HIV-M. tuberculosis-coinfected patients (81). Galectins such as Gal3 secrete into exosomes (82) and promote redox imbalance (83), whereas Gal9 is frequently found in the plasma of TB patients (84) and reactivates HIV-1 (71). While we have characterized the proteome of M. tuberculosis exosomes derived from macrophages, it is certain that the presence of immunomodulatory proteins, lipids, and RNA of M. tuberculosis also influences HIV-1 reactivation.…”

Section: Discussionmentioning

confidence: 99%

Mycobacterium tuberculosis Reactivates HIV-1 via Exosome-Mediated Resetting of Cellular Redox Potential and Bioenergetics

Tyagi

Pal

Agrawal

et al. 2020

mBio

View full text Add to dashboard Cite

The synergy between Mycobacterium tuberculosis and human immunodeficiency virus-1 (HIV-1) interferes with therapy and facilitates the pathogenesis of both human pathogens. Fundamental mechanisms by which M. tuberculosis exacerbates HIV-1 infection are not clear. Here, we show that exosomes secreted by macrophages infected with M. tuberculosis, including drug-resistant clinical strains, reactivated HIV-1 by inducing oxidative stress. Mechanistically, M. tuberculosis-specific exosomes realigned mitochondrial and nonmitochondrial oxygen consumption rates (OCR) and modulated the expression of host genes mediating oxidative stress response, inflammation, and HIV-1 transactivation. Proteomics analyses revealed the enrichment of several host factors (e.g., HIF-1␣, galectins, and Hsp90) known to promote HIV-1 reactivation in M. tuberculosis-specific exosomes. Treatment with a known antioxidant-N-acetyl cysteine (NAC)-or with inhibitors of host factors-galectins and Hsp90 -attenuated HIV-1 reactivation by M. tuberculosis-specific exosomes. Our findings uncover new paradigms for understanding the redox and bioenergetics bases of HIV-M. tuberculosis coinfection, which will enable the design of effective therapeutic strategies. IMPORTANCE Globally, individuals coinfected with the AIDS virus (HIV-1) and with M. tuberculosis (causative agent of tuberculosis [TB]) pose major obstacles in the clinical management of both diseases. At the heart of this issue is the apparent synergy between the two human pathogens. On the one hand, mechanisms induced by HIV-1 for reactivation of TB in AIDS patients are well characterized. On the other hand, while clinical findings clearly identified TB as a risk factor for HIV-1 reactivation and associated mortality, basic mechanisms by which M. tuberculosis exacerbates HIV-1 replication and infection remain poorly characterized. The significance of our research is in identifying the role of fundamental mechanisms such as redox and energy metabolism in catalyzing HIV-M. tuberculosis synergy. The quantification of redox and respiratory parameters affected by M. tuberculosis in stimulating HIV-1 will greatly enhance our understanding of HIV-M. tuberculosis coinfection, leading to a wider impact on the biomedical research community and creating new translational opportunities.

show abstract

Section: Discussionmentioning

confidence: 99%

Mycobacterium tuberculosis Reactivates HIV-1 via Exosome-Mediated Resetting of Cellular Redox Potential and Bioenergetics

Tyagi

Pal

Agrawal

et al. 2020

mBio

View full text Add to dashboard Cite

show abstract

“…62 This has been confirmed by the absence of annexin-V on the surface of bona fide exosomes. 63 Galectin-3 was recently shown to be selectively sorted in exosomes through its interaction via a conserved P(S/T)AP motif on Tsg101, 64 which might also be considered, like Alix, 33,48 as being an adaptor for ubiquitin-independent ILV sorting. 66 (Figure 3).…”

Section: Relationships With Autophagy and Endosomal Microautophagymentioning

confidence: 99%

Exosomes: Revisiting their role as “garbage bags”

Vidal

2019

Traffic

115

View full text Add to dashboard Cite

In recent years, the term “extracellular vesicle” (EV) has been used to define different types of vesicles released by various cells. It includes plasma membrane‐derived vesicles (ectosomes/microvesicles) and endosome‐derived vesicles (exosomes). Although it remains difficult to evaluate the compartment of origin of the two kinds of vesicles once released, it is critical to discriminate these vesicles because their mode of biogenesis is probably directly related to their physiologic function and/or to the physio‐pathologic state of the producing cell. The purpose of this review is to specifically consider exosome secretion and its consequences in terms of a material loss for producing cells, rather than on the effects of exosomes once they are taken up by recipient cells. I especially describe one putative basic function of exosomes, that is, to convey material out of cells for off‐site degradation by recipient cells. As illustrated by some examples, these components could be evacuated from cells for various reasons, for example, to promote “differentiation” or enhance homeostatic responses. This basic function might explain why so many diseases have made use of the exosomal pathway during pathogenesis.

show abstract

“…HSP90 is abundantly present in the serum of HIV-TB co-infected patients [81]. Galectins such as Gal3 secretes in exosomes [82] and promotes redox imbalance [83], whereas Gal9 is frequently found in the plasma of TB patients [84] and reactivates HIV-1 [71]. While we have characterized the proteome of Mtb -exosomes derived from macrophages, it is certain that the presence of immuno-modulatory proteins, lipids, and RNA of Mtb will also influence HIV-1 reactivation.…”

Section: Discussionmentioning

confidence: 99%

Mycobacterium tuberculosis reactivates HIV via exosomes mediated resetting of cellular redox potential and bioenergetics

Tyagi¹,

Pal²,

Srinivasan³

et al. 2019

Preprint

View full text Add to dashboard Cite

The synergy betweenMycobacterium tuberculosis(Mtb) and HIV-1 interferes with therapy and facilitates pathogenesis of both human pathogens. Fundamental mechanisms by whichMtbexacerbates HIV-1 are not clear. Here, we show that exosomes secreted by macrophages infected withMtb, including drug-resistant clinical strains, reactivate HIV-1 by inducing oxidative stress. Mechanistically,Mtb-specific exosomes realign mitochondrial and non-mitochondrial oxygen consumption rate (OCR) and modulates the expression of genes mediating oxidative stress response, inflammation, and HIV-1 transactivation. Proteomics revealed the enrichment of several host factors (e.g.,HIF-1α, galectins, Hsp90) known to promote HIV-1 reactivation in theMtb-specific exosomes. Treatment with a known antioxidant, N-acetyl cysteine, or with the inhibitors of host factors galectins and Hsp90 attenuated HIV-1 reactivation byMtb-specific exosomes. Our findings uncovered new paradigms for understanding the redox and bioenergetics basis of HIV-TB co-infection, which will enable the design of effective therapeutic strategies.

show abstract

Molecular mechanism to recruit galectin-3 into multivesicular bodies for polarized exosomal secretion

Cited by 102 publications

References 87 publications

Mycobacterium tuberculosis Reactivates HIV-1 via Exosome-Mediated Resetting of Cellular Redox Potential and Bioenergetics

Mycobacterium tuberculosis Reactivates HIV-1 via Exosome-Mediated Resetting of Cellular Redox Potential and Bioenergetics

Exosomes: Revisiting their role as “garbage bags”

Mycobacterium tuberculosis reactivates HIV via exosomes mediated resetting of cellular redox potential and bioenergetics

Contact Info

Product

Resources

About