A time-course comparative clinical and immune response evaluation study between the human pathogenic Orientia tsutsugamushi strains: Karp and Gilliam in a rhesus macaque (Macaca mulatta) model
Background Scrub typhus is a vector-borne febrile illness caused by Orientia tsutsugamushi transmitted by the bite of Trombiculid mites. O. tsutsugamushi has a high genetic diversity and is increasingly recognized to have a wider global distribution than previously assumed. Methodology/principle fin...
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ftdoajarticles:oai:doaj.org/article:7cd89c684acd47b396ac81059b6f014f 2023-05-15T15:18:19+02:00 A time-course comparative clinical and immune response evaluation study between the human pathogenic Orientia tsutsugamushi strains: Karp and Gilliam in a rhesus macaque (Macaca mulatta) model Manutsanun Inthawong Piyanate Sunyakumthorn Sirima Wongwairot Tippawan Anantatat Susanna J. Dunachie Rawiwan Im-Erbsin James W. Jones Carl J. Mason Luis A. Lugo Stuart D. Blacksell Nicholas P. J. Day Piengchan Sonthayanon Allen L. Richards Daniel H. Paris 2022-08-01T00:00:00Z https://doaj.org/article/7cd89c684acd47b396ac81059b6f014f EN eng Public Library of Science (PLoS) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9352090/?tool=EBI https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 https://doaj.org/article/7cd89c684acd47b396ac81059b6f014f PLoS Neglected Tropical Diseases, Vol 16, Iss 8 (2022) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2022 ftdoajarticles 2022-12-30T22:46:33Z Background Scrub typhus is a vector-borne febrile illness caused by Orientia tsutsugamushi transmitted by the bite of Trombiculid mites. O. tsutsugamushi has a high genetic diversity and is increasingly recognized to have a wider global distribution than previously assumed. Methodology/principle findings We evaluated the clinical outcomes and host immune responses of the two most relevant human pathogenic strains of O. tsutsugamushi; Karp (n = 4) and Gilliam (n = 4) in a time-course study over 80 days post infection (dpi) in a standardized scrub typhus non-human primate rhesus macaque model. We observed distinct features in clinical progression and immune response between the two strains; Gilliam-infected macaques developed more pronounced systemic infection characterized by an earlier onset of bacteremia, lymph node enlargement, eschar lesions and higher inflammatory markers during the acute phase of infection, when compared to the Karp strain. C-reactive protein (CRP) plasma levels, interferon gamma (IFN-γ, interleukin-1 receptor antagonist (IL-1ra), IL-15 serum concentrations, CRP/IL10- and IFN-γ/IL-10 ratios correlated positively with bacterial load in blood, implying activation of the innate immune response and preferential development of a T helper-type 1 immune response. The O. tsutsugamushi-specific immune memory responses in cells isolated from skin and lymph nodes at 80 dpi were more markedly elevated in the Gilliam-infected macaques than in the Karp-infected group. The comparative cytokine response dynamics of both strains revealed significant up-regulation of IFN-γ, tumor necrosis factor (TNF), IL-15, IL-6, IL-18, regulatory IL-1ra, IL-10, IL-8 and granulocyte-colony-stimulating factor (G-CSF). These data suggest that the clinical outcomes and host immune responses to scrub typhus could be associated with counter balancing effects of pro- and anti-inflammatory cytokine-mediated responses. Currently, no data on characterized time-course comparisons of O. tsutsugamushi strains regarding measures of ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Manutsanun Inthawong Piyanate Sunyakumthorn Sirima Wongwairot Tippawan Anantatat Susanna J. Dunachie Rawiwan Im-Erbsin James W. Jones Carl J. Mason Luis A. Lugo Stuart D. Blacksell Nicholas P. J. Day Piengchan Sonthayanon Allen L. Richards Daniel H. Paris A time-course comparative clinical and immune response evaluation study between the human pathogenic Orientia tsutsugamushi strains: Karp and Gilliam in a rhesus macaque (Macaca mulatta) model |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Background Scrub typhus is a vector-borne febrile illness caused by Orientia tsutsugamushi transmitted by the bite of Trombiculid mites. O. tsutsugamushi has a high genetic diversity and is increasingly recognized to have a wider global distribution than previously assumed. Methodology/principle findings We evaluated the clinical outcomes and host immune responses of the two most relevant human pathogenic strains of O. tsutsugamushi; Karp (n = 4) and Gilliam (n = 4) in a time-course study over 80 days post infection (dpi) in a standardized scrub typhus non-human primate rhesus macaque model. We observed distinct features in clinical progression and immune response between the two strains; Gilliam-infected macaques developed more pronounced systemic infection characterized by an earlier onset of bacteremia, lymph node enlargement, eschar lesions and higher inflammatory markers during the acute phase of infection, when compared to the Karp strain. C-reactive protein (CRP) plasma levels, interferon gamma (IFN-γ, interleukin-1 receptor antagonist (IL-1ra), IL-15 serum concentrations, CRP/IL10- and IFN-γ/IL-10 ratios correlated positively with bacterial load in blood, implying activation of the innate immune response and preferential development of a T helper-type 1 immune response. The O. tsutsugamushi-specific immune memory responses in cells isolated from skin and lymph nodes at 80 dpi were more markedly elevated in the Gilliam-infected macaques than in the Karp-infected group. The comparative cytokine response dynamics of both strains revealed significant up-regulation of IFN-γ, tumor necrosis factor (TNF), IL-15, IL-6, IL-18, regulatory IL-1ra, IL-10, IL-8 and granulocyte-colony-stimulating factor (G-CSF). These data suggest that the clinical outcomes and host immune responses to scrub typhus could be associated with counter balancing effects of pro- and anti-inflammatory cytokine-mediated responses. Currently, no data on characterized time-course comparisons of O. tsutsugamushi strains regarding measures of ... |
format |
Article in Journal/Newspaper |
author |
Manutsanun Inthawong Piyanate Sunyakumthorn Sirima Wongwairot Tippawan Anantatat Susanna J. Dunachie Rawiwan Im-Erbsin James W. Jones Carl J. Mason Luis A. Lugo Stuart D. Blacksell Nicholas P. J. Day Piengchan Sonthayanon Allen L. Richards Daniel H. Paris |
author_facet |
Manutsanun Inthawong Piyanate Sunyakumthorn Sirima Wongwairot Tippawan Anantatat Susanna J. Dunachie Rawiwan Im-Erbsin James W. Jones Carl J. Mason Luis A. Lugo Stuart D. Blacksell Nicholas P. J. Day Piengchan Sonthayanon Allen L. Richards Daniel H. Paris |
author_sort |
Manutsanun Inthawong |
title |
A time-course comparative clinical and immune response evaluation study between the human pathogenic Orientia tsutsugamushi strains: Karp and Gilliam in a rhesus macaque (Macaca mulatta) model |
title_short |
A time-course comparative clinical and immune response evaluation study between the human pathogenic Orientia tsutsugamushi strains: Karp and Gilliam in a rhesus macaque (Macaca mulatta) model |
title_full |
A time-course comparative clinical and immune response evaluation study between the human pathogenic Orientia tsutsugamushi strains: Karp and Gilliam in a rhesus macaque (Macaca mulatta) model |
title_fullStr |
A time-course comparative clinical and immune response evaluation study between the human pathogenic Orientia tsutsugamushi strains: Karp and Gilliam in a rhesus macaque (Macaca mulatta) model |
title_full_unstemmed |
A time-course comparative clinical and immune response evaluation study between the human pathogenic Orientia tsutsugamushi strains: Karp and Gilliam in a rhesus macaque (Macaca mulatta) model |
title_sort |
time-course comparative clinical and immune response evaluation study between the human pathogenic orientia tsutsugamushi strains: karp and gilliam in a rhesus macaque (macaca mulatta) model |
publisher |
Public Library of Science (PLoS) |
publishDate |
2022 |
url |
https://doaj.org/article/7cd89c684acd47b396ac81059b6f014f |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 16, Iss 8 (2022) |
op_relation |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9352090/?tool=EBI https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 https://doaj.org/article/7cd89c684acd47b396ac81059b6f014f |
_version_ |
1766348520121434112 |