Neutrophil-dendritic cell interaction plays an important role in live attenuated Leishmania vaccine induced immunity.
Background Neutrophils are involved in the initial host responses to pathogens. Neutrophils can activate T cell responses either independently or through indirect involvement of Dendritic cells (DCs). Recently we have demonstrated direct neutrophil-T cell interactions that initiate adaptive immune r...
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ftdoajarticles:oai:doaj.org/article:2d1df771608e44698a707b8c704a0dad 2023-05-15T15:13:52+02:00 Neutrophil-dendritic cell interaction plays an important role in live attenuated Leishmania vaccine induced immunity. Parna Bhattacharya Nevien Ismail Ankit Saxena Sreenivas Gannavaram Ranadhir Dey Timur Oljuskin Adovi Akue Kazuyo Takeda James Yu Subir Karmakar Pradeep K Dagur John Philip McCoy Hira L Nakhasi 2022-02-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0010224 https://doaj.org/article/2d1df771608e44698a707b8c704a0dad EN eng Public Library of Science (PLoS) https://doi.org/10.1371/journal.pntd.0010224 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0010224 https://doaj.org/article/2d1df771608e44698a707b8c704a0dad PLoS Neglected Tropical Diseases, Vol 16, Iss 2, p e0010224 (2022) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2022 ftdoajarticles https://doi.org/10.1371/journal.pntd.0010224 2022-12-31T00:25:56Z Background Neutrophils are involved in the initial host responses to pathogens. Neutrophils can activate T cell responses either independently or through indirect involvement of Dendritic cells (DCs). Recently we have demonstrated direct neutrophil-T cell interactions that initiate adaptive immune responses following immunization with live attenuated Leishmania donovani centrin deleted parasite vaccine (LdCen-/-). However, neutrophil-DC interactions in T cell priming in vaccine immunity in general are not known. In this study we evaluated the interaction between neutrophils and DCs during LdCen-/- infection and compared with wild type parasite (LdWT) both in vitro and in vivo. Methodology/findings LdCen-/- parasite induced increased expression of CCL3 in neutrophils caused higher recruitment of DCs capable of inducing a strong proinflammatory response and elevated co-stimulatory molecule expression compared to LdWT infection. To further illustrate neutrophil-DCs interactions in vivo, we infected LYS-eGFP mice with red fluorescent LdWT/LdCen-/- parasites and sort selected DCs that engulfed the neutrophil containing parasites or DCs that acquired the parasites directly in the ear draining lymph nodes (dLN) 5d post infection. The DCs predominantly acquired the parasites by phagocytosing infected neutrophils. Specifically, DCs containing LdCen-/- parasitized neutrophils exhibited a proinflammatory phenotype, increased expression of costimulatory molecules and initiated higher CD4+T cell priming ex-vivo. Notably, potent DC activation occurred when LdCen-/- parasites were acquired indirectly via engulfment of parasitized neutrophils compared to direct engulfment of LdCen-/- parasites by DCs. Neutrophil depletion in LdCen-/- infected mice significantly abrogated expression of CCL3 resulting in decreased DC recruitment in ear dLN. This event led to poor CD4+Th1 cell priming ex vivo that correlated with attenuated Tbet expression in ear dLN derived CD4+ T cells in vivo. Conclusions Collectively, LdCen-/- containing ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 16 2 e0010224 |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
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English |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Parna Bhattacharya Nevien Ismail Ankit Saxena Sreenivas Gannavaram Ranadhir Dey Timur Oljuskin Adovi Akue Kazuyo Takeda James Yu Subir Karmakar Pradeep K Dagur John Philip McCoy Hira L Nakhasi Neutrophil-dendritic cell interaction plays an important role in live attenuated Leishmania vaccine induced immunity. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Background Neutrophils are involved in the initial host responses to pathogens. Neutrophils can activate T cell responses either independently or through indirect involvement of Dendritic cells (DCs). Recently we have demonstrated direct neutrophil-T cell interactions that initiate adaptive immune responses following immunization with live attenuated Leishmania donovani centrin deleted parasite vaccine (LdCen-/-). However, neutrophil-DC interactions in T cell priming in vaccine immunity in general are not known. In this study we evaluated the interaction between neutrophils and DCs during LdCen-/- infection and compared with wild type parasite (LdWT) both in vitro and in vivo. Methodology/findings LdCen-/- parasite induced increased expression of CCL3 in neutrophils caused higher recruitment of DCs capable of inducing a strong proinflammatory response and elevated co-stimulatory molecule expression compared to LdWT infection. To further illustrate neutrophil-DCs interactions in vivo, we infected LYS-eGFP mice with red fluorescent LdWT/LdCen-/- parasites and sort selected DCs that engulfed the neutrophil containing parasites or DCs that acquired the parasites directly in the ear draining lymph nodes (dLN) 5d post infection. The DCs predominantly acquired the parasites by phagocytosing infected neutrophils. Specifically, DCs containing LdCen-/- parasitized neutrophils exhibited a proinflammatory phenotype, increased expression of costimulatory molecules and initiated higher CD4+T cell priming ex-vivo. Notably, potent DC activation occurred when LdCen-/- parasites were acquired indirectly via engulfment of parasitized neutrophils compared to direct engulfment of LdCen-/- parasites by DCs. Neutrophil depletion in LdCen-/- infected mice significantly abrogated expression of CCL3 resulting in decreased DC recruitment in ear dLN. This event led to poor CD4+Th1 cell priming ex vivo that correlated with attenuated Tbet expression in ear dLN derived CD4+ T cells in vivo. Conclusions Collectively, LdCen-/- containing ... |
format |
Article in Journal/Newspaper |
author |
Parna Bhattacharya Nevien Ismail Ankit Saxena Sreenivas Gannavaram Ranadhir Dey Timur Oljuskin Adovi Akue Kazuyo Takeda James Yu Subir Karmakar Pradeep K Dagur John Philip McCoy Hira L Nakhasi |
author_facet |
Parna Bhattacharya Nevien Ismail Ankit Saxena Sreenivas Gannavaram Ranadhir Dey Timur Oljuskin Adovi Akue Kazuyo Takeda James Yu Subir Karmakar Pradeep K Dagur John Philip McCoy Hira L Nakhasi |
author_sort |
Parna Bhattacharya |
title |
Neutrophil-dendritic cell interaction plays an important role in live attenuated Leishmania vaccine induced immunity. |
title_short |
Neutrophil-dendritic cell interaction plays an important role in live attenuated Leishmania vaccine induced immunity. |
title_full |
Neutrophil-dendritic cell interaction plays an important role in live attenuated Leishmania vaccine induced immunity. |
title_fullStr |
Neutrophil-dendritic cell interaction plays an important role in live attenuated Leishmania vaccine induced immunity. |
title_full_unstemmed |
Neutrophil-dendritic cell interaction plays an important role in live attenuated Leishmania vaccine induced immunity. |
title_sort |
neutrophil-dendritic cell interaction plays an important role in live attenuated leishmania vaccine induced immunity. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2022 |
url |
https://doi.org/10.1371/journal.pntd.0010224 https://doaj.org/article/2d1df771608e44698a707b8c704a0dad |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 16, Iss 2, p e0010224 (2022) |
op_relation |
https://doi.org/10.1371/journal.pntd.0010224 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0010224 https://doaj.org/article/2d1df771608e44698a707b8c704a0dad |
op_doi |
https://doi.org/10.1371/journal.pntd.0010224 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
16 |
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2 |
container_start_page |
e0010224 |
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1766344382789713920 |