Publication
Modulation of Cystatin F in Human Macrophages Impacts Cathepsin-Driven Killing of Multidrug-Resistant Mycobacterium tuberculosis
| dc.contributor.author | Mandal, Manoj | |
| dc.contributor.author | Pires, David | |
| dc.contributor.author | Catalão, Maria João | |
| dc.contributor.author | Azevedo-Pereira, José Miguel | |
| dc.contributor.author | Anes, Elsa | |
| dc.date.accessioned | 2023-08-24T15:18:19Z | |
| dc.date.available | 2023-08-24T15:18:19Z | |
| dc.date.issued | 2023-07-24 | |
| dc.date.updated | 2023-07-24T10:23:02Z | |
| dc.description.abstract | Tuberculosis (TB) treatment relies primarily on 70-year-old drugs, and prophylaxis suffers from the lack of an effective vaccine. Among the 10 million people exhibiting disease symptoms yearly, 450,000 have multidrug or extensively drug-resistant (MDR or XDR) TB. A greater understanding of host and pathogen interactions will lead to new therapeutic interventions for TB eradication. One of the strategies will be to target the host for better immune bactericidal responses against the TB causative agent Mycobacterium tuberculosis (Mtb). Cathepsins are promising targets due to their manipulation of Mtb with consequences such as decreased proteolytic activity and improved pathogen survival in macrophages. We recently demonstrated that we could overcome this enzymatic blockade by manipulating protease inhibitors such as cystatins. Here, we investigate the role of cystatin F, an inhibitor that we showed previously to be strongly upregulated during Mtb infection. Our results indicate that the silencing of cystatin F using siRNA increase the proteolytic activity of cathepsins S, L, and B, significantly impacting pathogen intracellular killing in macrophages. Taken together, these indicate the targeting of cystatin F as a potential adjuvant therapy for TB, including MDR and XDR-TB. | pt_PT |
| dc.description.sponsorship | This work was funded by Fundação para a Ciência e a Tecnologia (FCT)—grant numbers PTDC/SAU-INF/28182/2017 to E.A., EXPL/SAU-INF/0742/2021 to D.P., UIDB/04138/2020 to iMed-ULisboa, UIDB/04279/2020 to the Center for Interdisciplinary Research in Health and CEECINST/00070/2021 to Universidade Católica Portuguesa. M.M. is supported by a PhD fellowship from FCT with the reference 2021.07978.BD. | pt_PT |
| dc.description.version | info:eu-repo/semantics/publishedVersion | pt_PT |
| dc.identifier.citation | Mandal M, Pires D, Catalão MJ, Azevedo-Pereira JM, Anes E. Modulation of Cystatin F in Human Macrophages Impacts Cathepsin-Driven Killing of Multidrug-Resistant Mycobacterium tuberculosis. Microorganisms [Internet]. 2023 Jul 24;11(7):1861. Available from: http://dx.doi.org/10.3390/microorganisms11071861 | pt_PT |
| dc.identifier.doi | 10.3390/microorganisms11071861 | pt_PT |
| dc.identifier.slug | cv-prod-3308648 | |
| dc.identifier.uri | http://hdl.handle.net/10451/59005 | |
| dc.language.iso | eng | pt_PT |
| dc.peerreviewed | yes | pt_PT |
| dc.publisher | MDPI | pt_PT |
| dc.relation | CEECINST/00070/2021 | pt_PT |
| dc.relation | Development and validation of a 3D cell culture model of the tuberculosis granuloma that can be applied for drug discovery and host cellular studies in the context of a latent infection and multicellular immunologic response. | |
| dc.relation | Research Institute for Medicines | |
| dc.relation | Center for Interdisciplinary Research in Health | |
| dc.relation.publisherversion | https://www.mdpi.com/2076-2607/11/7/1861 | pt_PT |
| dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | pt_PT |
| dc.subject | tuberculosis | pt_PT |
| dc.subject | multidrug-resistant TB | pt_PT |
| dc.subject | cathepsins | pt_PT |
| dc.subject | cystatins | pt_PT |
| dc.subject | host-directed therapies | pt_PT |
| dc.title | Modulation of Cystatin F in Human Macrophages Impacts Cathepsin-Driven Killing of Multidrug-Resistant Mycobacterium tuberculosis | pt_PT |
| dc.type | journal article | |
| dspace.entity.type | Publication | |
| oaire.awardTitle | Development and validation of a 3D cell culture model of the tuberculosis granuloma that can be applied for drug discovery and host cellular studies in the context of a latent infection and multicellular immunologic response. | |
| oaire.awardTitle | Research Institute for Medicines | |
| oaire.awardTitle | Center for Interdisciplinary Research in Health | |
| oaire.awardURI | info:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FSAU-INF%2F28182%2F2017/PT | |
| oaire.awardURI | info:eu-repo/grantAgreement/FCT/3599-PPCDT/EXPL%2FSAU-INF%2F0742%2F2021/PT | |
| oaire.awardURI | info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F04138%2F2020/PT | |
| oaire.awardURI | info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F04279%2F2020/PT | |
| oaire.citation.issue | 7 | pt_PT |
| oaire.citation.startPage | 1861 | pt_PT |
| oaire.citation.title | Microorganisms | pt_PT |
| oaire.citation.volume | 11 | pt_PT |
| oaire.fundingStream | 3599-PPCDT | |
| oaire.fundingStream | 3599-PPCDT | |
| oaire.fundingStream | 6817 - DCRRNI ID | |
| oaire.fundingStream | 6817 - DCRRNI ID | |
| person.familyName | Mandal | |
| person.familyName | RODRIGUES PIRES | |
| person.familyName | Gracias Fernandes da Costa Catalão | |
| person.familyName | Azevedo Pereira | |
| person.familyName | RIBEIRO DOS SANTOS ANES | |
| person.givenName | Manoj Kumar | |
| person.givenName | DAVID ALEXANDRE | |
| person.givenName | Maria João | |
| person.givenName | José Miguel | |
| person.givenName | ELSA MARIA | |
| person.identifier | D-8245-2012 | |
| person.identifier | B-6731-2017 | |
| person.identifier | K-3124-2013 | |
| person.identifier.ciencia-id | 7219-8D5B-BFAB | |
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| person.identifier.ciencia-id | 1A10-7DAD-D860 | |
| person.identifier.orcid | 0000-0003-3997-9618 | |
| person.identifier.orcid | 0000-0001-9602-1516 | |
| person.identifier.orcid | 0000-0002-3794-457X | |
| person.identifier.orcid | 0000-0001-7434-7208 | |
| person.identifier.orcid | 0000-0001-5934-0198 | |
| person.identifier.scopus-author-id | 57222736661 | |
| person.identifier.scopus-author-id | 50162243000 | |
| person.identifier.scopus-author-id | 24447855200 | |
| person.identifier.scopus-author-id | 6506539639 | |
| person.identifier.scopus-author-id | 6507064447 | |
| project.funder.identifier | http://doi.org/10.13039/501100001871 | |
| project.funder.identifier | http://doi.org/10.13039/501100001871 | |
| project.funder.identifier | http://doi.org/10.13039/501100001871 | |
| project.funder.identifier | http://doi.org/10.13039/501100001871 | |
| project.funder.name | Fundação para a Ciência e a Tecnologia | |
| project.funder.name | Fundação para a Ciência e a Tecnologia | |
| project.funder.name | Fundação para a Ciência e a Tecnologia | |
| project.funder.name | Fundação para a Ciência e a Tecnologia | |
| rcaap.cv.cienciaid | 1A10-7DAD-D860 | ELSA MARIA RIBEIRO DOS SANTOS ANES | |
| rcaap.rights | openAccess | pt_PT |
| rcaap.type | article | pt_PT |
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