PGL I expression in live bacteria allows activation of a CD206/PPARγ cross-talk that may contribute to successful Mycobacterium leprae colonization of peripheral nerves.
Mycobacterium leprae, an obligate intracellular bacillus, infects Schwann cells (SCs), leading to peripheral nerve damage, the most severe leprosy symptom. In the present study, we revisited the involvement of phenolic glycolipid I (PGL I), an abundant, private, surface M. leprae molecule, in M. lep...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2018-07-01
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| Series: | PLoS Pathogens |
| Online Access: | http://europepmc.org/articles/PMC6056075?pdf=render |
| _version_ | 1818331697946558464 |
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| author | Chyntia Carolina Díaz Acosta André Alves Dias Thabatta Leal Silveira Andrezo Rosa Leonardo Ribeiro Batista-Silva Patricia Sammarco Rosa Thiago Gomes Toledo-Pinto Fabrício da Mota Ramalho Costa Flávio Alves Lara Luciana Silva Rodrigues Katherine Antunes Mattos Euzenir Nunes Sarno Patrícia Torres Bozza Christophe Guilhot Márcia de Berrêdo-Pinho Maria Cristina Vidal Pessolani |
| author_facet | Chyntia Carolina Díaz Acosta André Alves Dias Thabatta Leal Silveira Andrezo Rosa Leonardo Ribeiro Batista-Silva Patricia Sammarco Rosa Thiago Gomes Toledo-Pinto Fabrício da Mota Ramalho Costa Flávio Alves Lara Luciana Silva Rodrigues Katherine Antunes Mattos Euzenir Nunes Sarno Patrícia Torres Bozza Christophe Guilhot Márcia de Berrêdo-Pinho Maria Cristina Vidal Pessolani |
| author_sort | Chyntia Carolina Díaz Acosta |
| collection | DOAJ |
| description | Mycobacterium leprae, an obligate intracellular bacillus, infects Schwann cells (SCs), leading to peripheral nerve damage, the most severe leprosy symptom. In the present study, we revisited the involvement of phenolic glycolipid I (PGL I), an abundant, private, surface M. leprae molecule, in M. leprae-SC interaction by using a recombinant strain of M. bovis BCG engineered to express this glycolipid. We demonstrate that PGL I is essential for bacterial adhesion and SC internalization. We also show that live mycobacterium-producing PGL I induces the expression of the endocytic mannose receptor (MR/CD206) in infected cells in a peroxisome proliferator-activated receptor gamma (PPARγ)-dependent manner. Of note, blocking mannose recognition decreased bacterial entry and survival, pointing to a role for this alternative recognition pathway in bacterial pathogenesis in the nerve. Moreover, an active crosstalk between CD206 and the nuclear receptor PPARγ was detected that led to the induction of lipid droplets (LDs) formation and prostaglandin E2 (PGE2), previously described as fundamental players in bacterial pathogenesis. Finally, this pathway was shown to induce IL-8 secretion. Altogether, our study provides evidence that the entry of live M. leprae through PGL I recognition modulates the SC phenotype, favoring intracellular bacterial persistence with the concomitant secretion of inflammatory mediators that may ultimately be involved in neuroinflammation. |
| first_indexed | 2024-12-13T13:23:59Z |
| format | Article |
| id | doaj.art-50ccf4712f614ee2b1a2e585d4e04a04 |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-13T13:23:59Z |
| publishDate | 2018-07-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-50ccf4712f614ee2b1a2e585d4e04a042022-12-21T23:44:21ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742018-07-01147e100715110.1371/journal.ppat.1007151PGL I expression in live bacteria allows activation of a CD206/PPARγ cross-talk that may contribute to successful Mycobacterium leprae colonization of peripheral nerves.Chyntia Carolina Díaz AcostaAndré Alves DiasThabatta Leal Silveira Andrezo RosaLeonardo Ribeiro Batista-SilvaPatricia Sammarco RosaThiago Gomes Toledo-PintoFabrício da Mota Ramalho CostaFlávio Alves LaraLuciana Silva RodriguesKatherine Antunes MattosEuzenir Nunes SarnoPatrícia Torres BozzaChristophe GuilhotMárcia de Berrêdo-PinhoMaria Cristina Vidal PessolaniMycobacterium leprae, an obligate intracellular bacillus, infects Schwann cells (SCs), leading to peripheral nerve damage, the most severe leprosy symptom. In the present study, we revisited the involvement of phenolic glycolipid I (PGL I), an abundant, private, surface M. leprae molecule, in M. leprae-SC interaction by using a recombinant strain of M. bovis BCG engineered to express this glycolipid. We demonstrate that PGL I is essential for bacterial adhesion and SC internalization. We also show that live mycobacterium-producing PGL I induces the expression of the endocytic mannose receptor (MR/CD206) in infected cells in a peroxisome proliferator-activated receptor gamma (PPARγ)-dependent manner. Of note, blocking mannose recognition decreased bacterial entry and survival, pointing to a role for this alternative recognition pathway in bacterial pathogenesis in the nerve. Moreover, an active crosstalk between CD206 and the nuclear receptor PPARγ was detected that led to the induction of lipid droplets (LDs) formation and prostaglandin E2 (PGE2), previously described as fundamental players in bacterial pathogenesis. Finally, this pathway was shown to induce IL-8 secretion. Altogether, our study provides evidence that the entry of live M. leprae through PGL I recognition modulates the SC phenotype, favoring intracellular bacterial persistence with the concomitant secretion of inflammatory mediators that may ultimately be involved in neuroinflammation.http://europepmc.org/articles/PMC6056075?pdf=render |
| spellingShingle | Chyntia Carolina Díaz Acosta André Alves Dias Thabatta Leal Silveira Andrezo Rosa Leonardo Ribeiro Batista-Silva Patricia Sammarco Rosa Thiago Gomes Toledo-Pinto Fabrício da Mota Ramalho Costa Flávio Alves Lara Luciana Silva Rodrigues Katherine Antunes Mattos Euzenir Nunes Sarno Patrícia Torres Bozza Christophe Guilhot Márcia de Berrêdo-Pinho Maria Cristina Vidal Pessolani PGL I expression in live bacteria allows activation of a CD206/PPARγ cross-talk that may contribute to successful Mycobacterium leprae colonization of peripheral nerves. PLoS Pathogens |
| title | PGL I expression in live bacteria allows activation of a CD206/PPARγ cross-talk that may contribute to successful Mycobacterium leprae colonization of peripheral nerves. |
| title_full | PGL I expression in live bacteria allows activation of a CD206/PPARγ cross-talk that may contribute to successful Mycobacterium leprae colonization of peripheral nerves. |
| title_fullStr | PGL I expression in live bacteria allows activation of a CD206/PPARγ cross-talk that may contribute to successful Mycobacterium leprae colonization of peripheral nerves. |
| title_full_unstemmed | PGL I expression in live bacteria allows activation of a CD206/PPARγ cross-talk that may contribute to successful Mycobacterium leprae colonization of peripheral nerves. |
| title_short | PGL I expression in live bacteria allows activation of a CD206/PPARγ cross-talk that may contribute to successful Mycobacterium leprae colonization of peripheral nerves. |
| title_sort | pgl i expression in live bacteria allows activation of a cd206 pparγ cross talk that may contribute to successful mycobacterium leprae colonization of peripheral nerves |
| url | http://europepmc.org/articles/PMC6056075?pdf=render |
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