A Murine Model of Waning Scrub Typhus Cross-Protection between Heterologous Strains of <i>Orientia tsutsugamushi</i>
<i>Orientia tsutsugamushi</i>, the etiologic agent of the life-threatening febrile disease scrub typhus, is an obligately intracellular small coccobacillary bacterium belonging to the family Rickettsiaceae and is transmitted by the parasitic larval stage of trombiculid mites. Progress to...
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MDPI AG
2022-04-01
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| Series: | Pathogens |
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| Online Access: | https://www.mdpi.com/2076-0817/11/5/512 |
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| author | Nicole L. Mendell Guang Xu Thomas R. Shelite Donald H. Bouyer David H. Walker |
| author_facet | Nicole L. Mendell Guang Xu Thomas R. Shelite Donald H. Bouyer David H. Walker |
| author_sort | Nicole L. Mendell |
| collection | DOAJ |
| description | <i>Orientia tsutsugamushi</i>, the etiologic agent of the life-threatening febrile disease scrub typhus, is an obligately intracellular small coccobacillary bacterium belonging to the family Rickettsiaceae and is transmitted by the parasitic larval stage of trombiculid mites. Progress towards a vaccine for protection against scrub typhus has been impeded by characteristics of the pathogen and the infection. There are numerous strains of <i>O. tsutsugamushi</i> in the Asia-Pacific region with geographical overlap. In human cases immunity has been described as poor against heterologous strains of the pathogen, as well as short-lived against the homologous strain, with a mean antibody reversion rate of less than one year. Animal models of cross-protection as well as of deterioration of this cross-protection are needed to enhance understanding of transient immunity to scrub typhus. To build upon current understanding of this ineffective protection we sought to utilize our recently developed models, sublethal intradermal infection followed by challenge via ordinarily lethal hematogenous dissemination. Mice that were initially infected sublethally with <i>O. tsutsugamushi</i> Gilliam strain and were challenged with an ordinarily lethal dose of heterologous Karp strain were protected from death by a robust immune response at one month after the primary infection as evidenced by an abundance of mononuclear cellular infiltrates in target organs such as lung, liver, and kidney; maintenance of body weight; and low bacterial loads in the organs. Waning protection from lethal Karp strain challenge indicated by weight loss mirroring that observed in naïve mice was observed as early as 9 months after primary Gilliam strain infection, and higher bacterial loads, severe disease, and eventual death in some mice was observed after challenge with Karp strain at 14 months post-initial heterologous infection. |
| first_indexed | 2024-03-10T03:12:50Z |
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| last_indexed | 2024-03-10T03:12:50Z |
| publishDate | 2022-04-01 |
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| spelling | doaj.art-e7191cea8fa041ad9c5ed391f26f9c652023-11-23T12:31:48ZengMDPI AGPathogens2076-08172022-04-0111551210.3390/pathogens11050512A Murine Model of Waning Scrub Typhus Cross-Protection between Heterologous Strains of <i>Orientia tsutsugamushi</i>Nicole L. Mendell0Guang Xu1Thomas R. Shelite2Donald H. Bouyer3David H. Walker4Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USACollege of Osteopathic Medicine, Marian University, Indianapolis, IN 46222, USADivision of Infectious Diseases, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX 77555, USADepartment of Pathology, Center for Biodefense and Emerging Infectious Diseases, Center for Tropical Diseases, Sealy Institute for Vaccine Development, Institute of Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX 77555, USADepartment of Pathology, Center for Biodefense and Emerging Infectious Diseases, Center for Tropical Diseases, Sealy Institute for Vaccine Development, Institute of Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX 77555, USA<i>Orientia tsutsugamushi</i>, the etiologic agent of the life-threatening febrile disease scrub typhus, is an obligately intracellular small coccobacillary bacterium belonging to the family Rickettsiaceae and is transmitted by the parasitic larval stage of trombiculid mites. Progress towards a vaccine for protection against scrub typhus has been impeded by characteristics of the pathogen and the infection. There are numerous strains of <i>O. tsutsugamushi</i> in the Asia-Pacific region with geographical overlap. In human cases immunity has been described as poor against heterologous strains of the pathogen, as well as short-lived against the homologous strain, with a mean antibody reversion rate of less than one year. Animal models of cross-protection as well as of deterioration of this cross-protection are needed to enhance understanding of transient immunity to scrub typhus. To build upon current understanding of this ineffective protection we sought to utilize our recently developed models, sublethal intradermal infection followed by challenge via ordinarily lethal hematogenous dissemination. Mice that were initially infected sublethally with <i>O. tsutsugamushi</i> Gilliam strain and were challenged with an ordinarily lethal dose of heterologous Karp strain were protected from death by a robust immune response at one month after the primary infection as evidenced by an abundance of mononuclear cellular infiltrates in target organs such as lung, liver, and kidney; maintenance of body weight; and low bacterial loads in the organs. Waning protection from lethal Karp strain challenge indicated by weight loss mirroring that observed in naïve mice was observed as early as 9 months after primary Gilliam strain infection, and higher bacterial loads, severe disease, and eventual death in some mice was observed after challenge with Karp strain at 14 months post-initial heterologous infection.https://www.mdpi.com/2076-0817/11/5/512<i>Orientia</i>scrub typhusintradermalhematogenous modelsublethalimmunity |
| spellingShingle | Nicole L. Mendell Guang Xu Thomas R. Shelite Donald H. Bouyer David H. Walker A Murine Model of Waning Scrub Typhus Cross-Protection between Heterologous Strains of <i>Orientia tsutsugamushi</i> Pathogens <i>Orientia</i> scrub typhus intradermal hematogenous model sublethal immunity |
| title | A Murine Model of Waning Scrub Typhus Cross-Protection between Heterologous Strains of <i>Orientia tsutsugamushi</i> |
| title_full | A Murine Model of Waning Scrub Typhus Cross-Protection between Heterologous Strains of <i>Orientia tsutsugamushi</i> |
| title_fullStr | A Murine Model of Waning Scrub Typhus Cross-Protection between Heterologous Strains of <i>Orientia tsutsugamushi</i> |
| title_full_unstemmed | A Murine Model of Waning Scrub Typhus Cross-Protection between Heterologous Strains of <i>Orientia tsutsugamushi</i> |
| title_short | A Murine Model of Waning Scrub Typhus Cross-Protection between Heterologous Strains of <i>Orientia tsutsugamushi</i> |
| title_sort | murine model of waning scrub typhus cross protection between heterologous strains of i orientia tsutsugamushi i |
| topic | <i>Orientia</i> scrub typhus intradermal hematogenous model sublethal immunity |
| url | https://www.mdpi.com/2076-0817/11/5/512 |
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