Leishmania major drives host phagocyte death and cell-to-cell transfer depending on intracellular pathogen proliferation rate
The virulence of intracellular pathogens relies largely on the ability to survive and replicate within phagocytes but also on release and transfer into new host cells. Such cell-to-cell transfer could represent a target for counteracting microbial pathogenesis. However, our understanding of the unde...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Clinical investigation
2023-07-01
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| Series: | JCI Insight |
| Subjects: | |
| Online Access: | https://doi.org/10.1172/jci.insight.169020 |
| _version_ | 1797634292117929984 |
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| author | Iris Baars Moritz Jaedtka Leon-Alexander Dewitz Yan Fu Tobias Franz Juliane Mohr Patricia Gintschel Hannes Berlin Angelina Degen Sandra Freier Stefan Rygol Burkhart Schraven Sascha Kahlfuß Ger van Zandbergen Andreas J. Müller |
| author_facet | Iris Baars Moritz Jaedtka Leon-Alexander Dewitz Yan Fu Tobias Franz Juliane Mohr Patricia Gintschel Hannes Berlin Angelina Degen Sandra Freier Stefan Rygol Burkhart Schraven Sascha Kahlfuß Ger van Zandbergen Andreas J. Müller |
| author_sort | Iris Baars |
| collection | DOAJ |
| description | The virulence of intracellular pathogens relies largely on the ability to survive and replicate within phagocytes but also on release and transfer into new host cells. Such cell-to-cell transfer could represent a target for counteracting microbial pathogenesis. However, our understanding of the underlying cellular and molecular processes remains woefully insufficient. Using intravital 2-photon microscopy of caspase-3 activation in the Leishmania major–infected (L. major–infected) live skin, we showed increased apoptosis in cells infected by the parasite. Also, transfer of the parasite to new host cells occurred directly without a detectable extracellular state and was associated with concomitant uptake of cellular material from the original host cell. These in vivo findings were fully recapitulated in infections of isolated human phagocytes. Furthermore, we observed that high pathogen proliferation increased cell death in infected cells, and long-term residency within an infected host cell was only possible for slowly proliferating parasites. Our results therefore suggest that L. major drives its own dissemination to new phagocytes by inducing host cell death in a proliferation-dependent manner. |
| first_indexed | 2024-03-11T12:05:34Z |
| format | Article |
| id | doaj.art-50f6bbf74d0449dca586aefd281cb8f2 |
| institution | Directory Open Access Journal |
| issn | 2379-3708 |
| language | English |
| last_indexed | 2024-03-11T12:05:34Z |
| publishDate | 2023-07-01 |
| publisher | American Society for Clinical investigation |
| record_format | Article |
| series | JCI Insight |
| spelling | doaj.art-50f6bbf74d0449dca586aefd281cb8f22023-11-07T16:25:54ZengAmerican Society for Clinical investigationJCI Insight2379-37082023-07-01814Leishmania major drives host phagocyte death and cell-to-cell transfer depending on intracellular pathogen proliferation rateIris BaarsMoritz JaedtkaLeon-Alexander DewitzYan FuTobias FranzJuliane MohrPatricia GintschelHannes BerlinAngelina DegenSandra FreierStefan RygolBurkhart SchravenSascha KahlfußGer van ZandbergenAndreas J. MüllerThe virulence of intracellular pathogens relies largely on the ability to survive and replicate within phagocytes but also on release and transfer into new host cells. Such cell-to-cell transfer could represent a target for counteracting microbial pathogenesis. However, our understanding of the underlying cellular and molecular processes remains woefully insufficient. Using intravital 2-photon microscopy of caspase-3 activation in the Leishmania major–infected (L. major–infected) live skin, we showed increased apoptosis in cells infected by the parasite. Also, transfer of the parasite to new host cells occurred directly without a detectable extracellular state and was associated with concomitant uptake of cellular material from the original host cell. These in vivo findings were fully recapitulated in infections of isolated human phagocytes. Furthermore, we observed that high pathogen proliferation increased cell death in infected cells, and long-term residency within an infected host cell was only possible for slowly proliferating parasites. Our results therefore suggest that L. major drives its own dissemination to new phagocytes by inducing host cell death in a proliferation-dependent manner.https://doi.org/10.1172/jci.insight.169020Infectious diseaseMicrobiology |
| spellingShingle | Iris Baars Moritz Jaedtka Leon-Alexander Dewitz Yan Fu Tobias Franz Juliane Mohr Patricia Gintschel Hannes Berlin Angelina Degen Sandra Freier Stefan Rygol Burkhart Schraven Sascha Kahlfuß Ger van Zandbergen Andreas J. Müller Leishmania major drives host phagocyte death and cell-to-cell transfer depending on intracellular pathogen proliferation rate JCI Insight Infectious disease Microbiology |
| title | Leishmania major drives host phagocyte death and cell-to-cell transfer depending on intracellular pathogen proliferation rate |
| title_full | Leishmania major drives host phagocyte death and cell-to-cell transfer depending on intracellular pathogen proliferation rate |
| title_fullStr | Leishmania major drives host phagocyte death and cell-to-cell transfer depending on intracellular pathogen proliferation rate |
| title_full_unstemmed | Leishmania major drives host phagocyte death and cell-to-cell transfer depending on intracellular pathogen proliferation rate |
| title_short | Leishmania major drives host phagocyte death and cell-to-cell transfer depending on intracellular pathogen proliferation rate |
| title_sort | leishmania major drives host phagocyte death and cell to cell transfer depending on intracellular pathogen proliferation rate |
| topic | Infectious disease Microbiology |
| url | https://doi.org/10.1172/jci.insight.169020 |
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