Comparison of Lethal and Nonlethal Mouse Models of <i>Orientia tsutsugamushi</i> Infection Reveals T-Cell Population-Associated Cytokine Signatures Correlated with Lethality and Protection
The antigenic diversity of <i>Orientia tsutsugamushi</i> as well as the interstrain difference(s) associated with virulence in mice impose the necessity to dissect the host immune response. In this study we compared the host response in lethal and non-lethal murine models of <i>O....
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MDPI AG
2021-07-01
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| Series: | Tropical Medicine and Infectious Disease |
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| Online Access: | https://www.mdpi.com/2414-6366/6/3/121 |
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| author | Alison Luce-Fedrow Suchismita Chattopadhyay Teik-Chye Chan Gregory Pearson John B. Patton Allen L. Richards |
| author_facet | Alison Luce-Fedrow Suchismita Chattopadhyay Teik-Chye Chan Gregory Pearson John B. Patton Allen L. Richards |
| author_sort | Alison Luce-Fedrow |
| collection | DOAJ |
| description | The antigenic diversity of <i>Orientia tsutsugamushi</i> as well as the interstrain difference(s) associated with virulence in mice impose the necessity to dissect the host immune response. In this study we compared the host response in lethal and non-lethal murine models of <i>O. tsutsugamushi</i> infection using the two strains, Karp (New Guinea) and Woods (Australia). The models included the lethal model: Karp intraperitoneal (IP) challenge; and the nonlethal models: Karp intradermal (ID), Woods IP, and Woods ID challenges. We monitored bacterial trafficking to the liver, lung, spleen, kidney, heart, and blood, and seroconversion during the 21-day challenge. Bacterial trafficking to all organs was observed in both the lethal and nonlethal models of infection, with significant increases in average bacterial loads observed in the livers and hearts of the lethal model. Multicolor flow cytometry was utilized to analyze the CD4+ and CD8+ T cell populations and their intracellular production of the cytokines IFNγ, TNF, and IL2 (single, double, and triple combinations) associated with both the lethal and nonlethal murine models of infection. The lethal model was defined by a cytokine signature of double- (IFNγ-IL2) and triple-producing (IL2-TNF-IFNγ) CD4+ T-cell populations; no multifunctional signature was identified in the CD8+ T-cell populations associated with the lethal model. In the nonlethal model, the cytokine signature was predominated by CD4+ and CD8+ T-cell populations associated with single (IL2) and/or double (IL2-TNF) populations of producers. The cytokine signatures associated with our lethal model will become depletion targets in future experiments; those signatures associated with our nonlethal model are hypothesized to be related to the protective nature of the nonlethal challenges. |
| first_indexed | 2024-03-10T07:10:11Z |
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| issn | 2414-6366 |
| language | English |
| last_indexed | 2024-03-10T07:10:11Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Tropical Medicine and Infectious Disease |
| spelling | doaj.art-fea17cc441324a2792cc8ab6d549d87c2023-11-22T15:32:00ZengMDPI AGTropical Medicine and Infectious Disease2414-63662021-07-016312110.3390/tropicalmed6030121Comparison of Lethal and Nonlethal Mouse Models of <i>Orientia tsutsugamushi</i> Infection Reveals T-Cell Population-Associated Cytokine Signatures Correlated with Lethality and ProtectionAlison Luce-Fedrow0Suchismita Chattopadhyay1Teik-Chye Chan2Gregory Pearson3John B. Patton4Allen L. Richards5Department of Viral and Rickettsial Diseases, Naval Medical Research Center, Silver Spring, MD 20910, USADepartment of Viral and Rickettsial Diseases, Naval Medical Research Center, Silver Spring, MD 20910, USADepartment of Viral and Rickettsial Diseases, Naval Medical Research Center, Silver Spring, MD 20910, USADepartment of Biology, Shippensburg University, Shippensburg, PA 17257, USADepartment of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, PA 19107, USADepartment of Viral and Rickettsial Diseases, Naval Medical Research Center, Silver Spring, MD 20910, USAThe antigenic diversity of <i>Orientia tsutsugamushi</i> as well as the interstrain difference(s) associated with virulence in mice impose the necessity to dissect the host immune response. In this study we compared the host response in lethal and non-lethal murine models of <i>O. tsutsugamushi</i> infection using the two strains, Karp (New Guinea) and Woods (Australia). The models included the lethal model: Karp intraperitoneal (IP) challenge; and the nonlethal models: Karp intradermal (ID), Woods IP, and Woods ID challenges. We monitored bacterial trafficking to the liver, lung, spleen, kidney, heart, and blood, and seroconversion during the 21-day challenge. Bacterial trafficking to all organs was observed in both the lethal and nonlethal models of infection, with significant increases in average bacterial loads observed in the livers and hearts of the lethal model. Multicolor flow cytometry was utilized to analyze the CD4+ and CD8+ T cell populations and their intracellular production of the cytokines IFNγ, TNF, and IL2 (single, double, and triple combinations) associated with both the lethal and nonlethal murine models of infection. The lethal model was defined by a cytokine signature of double- (IFNγ-IL2) and triple-producing (IL2-TNF-IFNγ) CD4+ T-cell populations; no multifunctional signature was identified in the CD8+ T-cell populations associated with the lethal model. In the nonlethal model, the cytokine signature was predominated by CD4+ and CD8+ T-cell populations associated with single (IL2) and/or double (IL2-TNF) populations of producers. The cytokine signatures associated with our lethal model will become depletion targets in future experiments; those signatures associated with our nonlethal model are hypothesized to be related to the protective nature of the nonlethal challenges.https://www.mdpi.com/2414-6366/6/3/121scrub typhus<i>Orientia tsutsugamushi</i>mouse modelT cellscytokineslethality |
| spellingShingle | Alison Luce-Fedrow Suchismita Chattopadhyay Teik-Chye Chan Gregory Pearson John B. Patton Allen L. Richards Comparison of Lethal and Nonlethal Mouse Models of <i>Orientia tsutsugamushi</i> Infection Reveals T-Cell Population-Associated Cytokine Signatures Correlated with Lethality and Protection Tropical Medicine and Infectious Disease scrub typhus <i>Orientia tsutsugamushi</i> mouse model T cells cytokines lethality |
| title | Comparison of Lethal and Nonlethal Mouse Models of <i>Orientia tsutsugamushi</i> Infection Reveals T-Cell Population-Associated Cytokine Signatures Correlated with Lethality and Protection |
| title_full | Comparison of Lethal and Nonlethal Mouse Models of <i>Orientia tsutsugamushi</i> Infection Reveals T-Cell Population-Associated Cytokine Signatures Correlated with Lethality and Protection |
| title_fullStr | Comparison of Lethal and Nonlethal Mouse Models of <i>Orientia tsutsugamushi</i> Infection Reveals T-Cell Population-Associated Cytokine Signatures Correlated with Lethality and Protection |
| title_full_unstemmed | Comparison of Lethal and Nonlethal Mouse Models of <i>Orientia tsutsugamushi</i> Infection Reveals T-Cell Population-Associated Cytokine Signatures Correlated with Lethality and Protection |
| title_short | Comparison of Lethal and Nonlethal Mouse Models of <i>Orientia tsutsugamushi</i> Infection Reveals T-Cell Population-Associated Cytokine Signatures Correlated with Lethality and Protection |
| title_sort | comparison of lethal and nonlethal mouse models of i orientia tsutsugamushi i infection reveals t cell population associated cytokine signatures correlated with lethality and protection |
| topic | scrub typhus <i>Orientia tsutsugamushi</i> mouse model T cells cytokines lethality |
| url | https://www.mdpi.com/2414-6366/6/3/121 |
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