Establishment of a Rhesus Macaque Model for Scrub Typhus Transmission: Pilot Study to Evaluate the Minimal <i>Orientia tsutsugamushi</i> Transmission Time by <i>Leptotrombidium</i> <i>chiangraiensis</i> Chiggers
Recently, an intradermal inoculation of the rhesus macaque model of scrub typhus has been characterized at our institution. The current project was to establish a rhesus macaque model of scrub typhus using the naturally infected chigger challenge method that faithfully mimics the natural route of pa...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-08-01
|
| Series: | Pathogens |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-0817/10/8/1028 |
| _version_ | 1797522537409675264 |
|---|---|
| author | Piyada Linsuwanon Sirima Wongwairot Nutthanun Auysawasdi Taweesak Monkanna Allen L. Richards Surachai Leepitakrat Piyanate Sunyakumthorn Rawiwan Im-Erbsin Katie Poole-Smith Patrick McCardle |
| author_facet | Piyada Linsuwanon Sirima Wongwairot Nutthanun Auysawasdi Taweesak Monkanna Allen L. Richards Surachai Leepitakrat Piyanate Sunyakumthorn Rawiwan Im-Erbsin Katie Poole-Smith Patrick McCardle |
| author_sort | Piyada Linsuwanon |
| collection | DOAJ |
| description | Recently, an intradermal inoculation of the rhesus macaque model of scrub typhus has been characterized at our institution. The current project was to establish a rhesus macaque model of scrub typhus using the naturally infected chigger challenge method that faithfully mimics the natural route of pathogen transmission to fully understand the host-pathogen-vector interactions influencing pathogen transmission. Unlike the needle-based inoculation route, <i>Orientia tsutsugamushi</i>-infected chiggers introduce both pathogen and chigger saliva into the host epidermis at the bite site. However, information on the interaction or influence of chigger saliva on pathogenesis and immunity of host has been limited, consequently hindering vaccine development and transmission-blocking studies. To characterize chigger inoculated <i>O. tsutsugamushi</i> in rhesus macaques, we determined the minimum chigger attachment time required to efficiently transmit <i>O. tsutsugamushi</i> to the immunocompetent hosts and preliminary assessed clinical parameters, course of bacterial infection, and host’s immunological response to identifying potential factors influencing pathogen infection. Chigger infestation on hosts resulted in: (i) Rapid transmission of <i>O. tsutsugamushi</i> within 1 h and (ii) antigen-specific type I and II T-cell responses were markedly increased during the acute phase of infection, suggesting that both systems play critical roles in response to the pathogen control during the primary infection. In summary, we demonstrate that <i>O. tsutsugamushi</i> infection in rhesus macaques via chigger challenge recapitulates the time of disease onset and bacteremia observed in scrub typhus patients. Levels of proinflammatory cytokines and chemokines were positively correlated with bacteremia. |
| first_indexed | 2024-03-10T08:29:51Z |
| format | Article |
| id | doaj.art-ffbb3049d9504845bc05043a27955e37 |
| institution | Directory Open Access Journal |
| issn | 2076-0817 |
| language | English |
| last_indexed | 2024-03-10T08:29:51Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pathogens |
| spelling | doaj.art-ffbb3049d9504845bc05043a27955e372023-11-22T09:09:42ZengMDPI AGPathogens2076-08172021-08-01108102810.3390/pathogens10081028Establishment of a Rhesus Macaque Model for Scrub Typhus Transmission: Pilot Study to Evaluate the Minimal <i>Orientia tsutsugamushi</i> Transmission Time by <i>Leptotrombidium</i> <i>chiangraiensis</i> ChiggersPiyada Linsuwanon0Sirima Wongwairot1Nutthanun Auysawasdi2Taweesak Monkanna3Allen L. Richards4Surachai Leepitakrat5Piyanate Sunyakumthorn6Rawiwan Im-Erbsin7Katie Poole-Smith8Patrick McCardle9Department of Entomology, USAMD-AFRIMS, Bangkok 10330, ThailandDepartment of Entomology, USAMD-AFRIMS, Bangkok 10330, ThailandDepartment of Entomology, USAMD-AFRIMS, Bangkok 10330, ThailandDepartment of Entomology, USAMD-AFRIMS, Bangkok 10330, ThailandDepartment of Preventive Medicine and Biostatistics, Uniformed Services University of Health Sciences, Bethesda, MD 20814, USADepartment of Entomology, USAMD-AFRIMS, Bangkok 10330, ThailandDepartment of Veterinary Medicine, USAMD-AFRIMS, Bangkok 10330, ThailandDepartment of Veterinary Medicine, USAMD-AFRIMS, Bangkok 10330, ThailandDepartment of Entomology, USAMD-AFRIMS, Bangkok 10330, ThailandDepartment of Entomology, USAMD-AFRIMS, Bangkok 10330, ThailandRecently, an intradermal inoculation of the rhesus macaque model of scrub typhus has been characterized at our institution. The current project was to establish a rhesus macaque model of scrub typhus using the naturally infected chigger challenge method that faithfully mimics the natural route of pathogen transmission to fully understand the host-pathogen-vector interactions influencing pathogen transmission. Unlike the needle-based inoculation route, <i>Orientia tsutsugamushi</i>-infected chiggers introduce both pathogen and chigger saliva into the host epidermis at the bite site. However, information on the interaction or influence of chigger saliva on pathogenesis and immunity of host has been limited, consequently hindering vaccine development and transmission-blocking studies. To characterize chigger inoculated <i>O. tsutsugamushi</i> in rhesus macaques, we determined the minimum chigger attachment time required to efficiently transmit <i>O. tsutsugamushi</i> to the immunocompetent hosts and preliminary assessed clinical parameters, course of bacterial infection, and host’s immunological response to identifying potential factors influencing pathogen infection. Chigger infestation on hosts resulted in: (i) Rapid transmission of <i>O. tsutsugamushi</i> within 1 h and (ii) antigen-specific type I and II T-cell responses were markedly increased during the acute phase of infection, suggesting that both systems play critical roles in response to the pathogen control during the primary infection. In summary, we demonstrate that <i>O. tsutsugamushi</i> infection in rhesus macaques via chigger challenge recapitulates the time of disease onset and bacteremia observed in scrub typhus patients. Levels of proinflammatory cytokines and chemokines were positively correlated with bacteremia.https://www.mdpi.com/2076-0817/10/8/1028scrub typhuschigger transmissionscrub typhus disease modeltransmission time |
| spellingShingle | Piyada Linsuwanon Sirima Wongwairot Nutthanun Auysawasdi Taweesak Monkanna Allen L. Richards Surachai Leepitakrat Piyanate Sunyakumthorn Rawiwan Im-Erbsin Katie Poole-Smith Patrick McCardle Establishment of a Rhesus Macaque Model for Scrub Typhus Transmission: Pilot Study to Evaluate the Minimal <i>Orientia tsutsugamushi</i> Transmission Time by <i>Leptotrombidium</i> <i>chiangraiensis</i> Chiggers Pathogens scrub typhus chigger transmission scrub typhus disease model transmission time |
| title | Establishment of a Rhesus Macaque Model for Scrub Typhus Transmission: Pilot Study to Evaluate the Minimal <i>Orientia tsutsugamushi</i> Transmission Time by <i>Leptotrombidium</i> <i>chiangraiensis</i> Chiggers |
| title_full | Establishment of a Rhesus Macaque Model for Scrub Typhus Transmission: Pilot Study to Evaluate the Minimal <i>Orientia tsutsugamushi</i> Transmission Time by <i>Leptotrombidium</i> <i>chiangraiensis</i> Chiggers |
| title_fullStr | Establishment of a Rhesus Macaque Model for Scrub Typhus Transmission: Pilot Study to Evaluate the Minimal <i>Orientia tsutsugamushi</i> Transmission Time by <i>Leptotrombidium</i> <i>chiangraiensis</i> Chiggers |
| title_full_unstemmed | Establishment of a Rhesus Macaque Model for Scrub Typhus Transmission: Pilot Study to Evaluate the Minimal <i>Orientia tsutsugamushi</i> Transmission Time by <i>Leptotrombidium</i> <i>chiangraiensis</i> Chiggers |
| title_short | Establishment of a Rhesus Macaque Model for Scrub Typhus Transmission: Pilot Study to Evaluate the Minimal <i>Orientia tsutsugamushi</i> Transmission Time by <i>Leptotrombidium</i> <i>chiangraiensis</i> Chiggers |
| title_sort | establishment of a rhesus macaque model for scrub typhus transmission pilot study to evaluate the minimal i orientia tsutsugamushi i transmission time by i leptotrombidium i i chiangraiensis i chiggers |
| topic | scrub typhus chigger transmission scrub typhus disease model transmission time |
| url | https://www.mdpi.com/2076-0817/10/8/1028 |
| work_keys_str_mv | AT piyadalinsuwanon establishmentofarhesusmacaquemodelforscrubtyphustransmissionpilotstudytoevaluatetheminimaliorientiatsutsugamushiitransmissiontimebyileptotrombidiumiichiangraiensisichiggers AT sirimawongwairot establishmentofarhesusmacaquemodelforscrubtyphustransmissionpilotstudytoevaluatetheminimaliorientiatsutsugamushiitransmissiontimebyileptotrombidiumiichiangraiensisichiggers AT nutthanunauysawasdi establishmentofarhesusmacaquemodelforscrubtyphustransmissionpilotstudytoevaluatetheminimaliorientiatsutsugamushiitransmissiontimebyileptotrombidiumiichiangraiensisichiggers AT taweesakmonkanna establishmentofarhesusmacaquemodelforscrubtyphustransmissionpilotstudytoevaluatetheminimaliorientiatsutsugamushiitransmissiontimebyileptotrombidiumiichiangraiensisichiggers AT allenlrichards establishmentofarhesusmacaquemodelforscrubtyphustransmissionpilotstudytoevaluatetheminimaliorientiatsutsugamushiitransmissiontimebyileptotrombidiumiichiangraiensisichiggers AT surachaileepitakrat establishmentofarhesusmacaquemodelforscrubtyphustransmissionpilotstudytoevaluatetheminimaliorientiatsutsugamushiitransmissiontimebyileptotrombidiumiichiangraiensisichiggers AT piyanatesunyakumthorn establishmentofarhesusmacaquemodelforscrubtyphustransmissionpilotstudytoevaluatetheminimaliorientiatsutsugamushiitransmissiontimebyileptotrombidiumiichiangraiensisichiggers AT rawiwanimerbsin establishmentofarhesusmacaquemodelforscrubtyphustransmissionpilotstudytoevaluatetheminimaliorientiatsutsugamushiitransmissiontimebyileptotrombidiumiichiangraiensisichiggers AT katiepoolesmith establishmentofarhesusmacaquemodelforscrubtyphustransmissionpilotstudytoevaluatetheminimaliorientiatsutsugamushiitransmissiontimebyileptotrombidiumiichiangraiensisichiggers AT patrickmccardle establishmentofarhesusmacaquemodelforscrubtyphustransmissionpilotstudytoevaluatetheminimaliorientiatsutsugamushiitransmissiontimebyileptotrombidiumiichiangraiensisichiggers |