Differential cellular immune responses against Orientia tsutsugamushi Karp and Gilliam strains following acute infection in mice

Article Microbiology

Orientia tsutsugamushi Infection Stimulates Syk-Dependent Responses and Innate Cytosolic Defenses in Macrophages

James Fisher et al.

Summary: This study demonstrates that Syk-dependent CLR receptors play a role in innate immune recognition and proinflammatory responses against O. tsutsugamushi.

PATHOGENS (2023)

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Article Infectious Diseases

Multiple Orientia clusters and Th1-skewed chemokine profile: a cross-sectional study in patients with scrub typhus from Nepal

Carina Chan-Song Muench et al.

Summary: This study investigates the genetic diversity of Orientia tsutsugamushi strains circulating in Nepal and explores the immunoregulatory responses in scrub typhus patients, revealing high heterogeneity and impaired immune responses.

INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES (2023)

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Article Infectious Diseases

A whole blood intracellular cytokine assay optimised for field site studies demonstrates polyfunctionality of CD4+T cells in acute scrub typhus

Manutsanun Inthawong et al.

Summary: The combination of intracellular cytokine staining and immunophenotyping using flow cytometry allows for the assessment of T cell phenotype and effector function in response to pathogens and vaccines. Whole blood samples can be used instead of peripheral blood mononuclear cells to avoid immediate processing and loss of functional antigen presenting cells. This study aims to provide a robust tool for the assessment of antigen-specific T cell responses in field site settings with limited resources.

PLOS NEGLECTED TROPICAL DISEASES (2023)

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Article Infectious Diseases

Genomic bacterial load associated with bacterial genotypes and clinical characteristics in patients with scrub typhus in Hainan Island, Southern China

Gaoyu Wang et al.

Summary: This study analyzed the blood samples of 117 surviving patients with scrub typhus who had not received appropriate antibiotic treatment and found that the bacterial DNA load of O. tsutsugamushi was associated with severity and genotype, but not with the number of dysfunctional organs, gender, age, presence of eschar, or the season of disease onset.

PLOS NEGLECTED TROPICAL DISEASES (2023)

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Article Immunology

Brain transcriptomics reveal the activation of neuroinflammation pathways during acute Orientia tsutsugamushi infection in mice

Yuejin Liang et al.

Summary: Scrub typhus, caused by Orientia tsutsugamushi (Ot), often involves the central nervous system (CNS). This study used a mouse model to investigate the brain transcriptome dynamics during severe scrub typhus and identified activated neuroinflammation pathways. The results revealed excessive immune signaling, inflammation, and blood-brain barrier dysregulation, along with microglial activation and proinflammatory cytokine production.

FRONTIERS IN IMMUNOLOGY (2023)

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Review Immunology

A scrub typhus vaccine presents a challenging unmet need

David H. Walker et al.

Summary: Scrub typhus, caused by Orientia tsutsugamushi, is a life-threatening febrile illness in eastern Asia and the Western Pacific and Indian oceans. Despite efforts to develop a vaccine for 80 years, there is still no effective vaccine available. The main challenge lies in understanding the immunity to O. tsutsugamushi.

NPJ VACCINES (2023)

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Review Microbiology

Orientia and Rickettsia: different flowers from the same garden

Joseph J. Gillespie et al.

Summary: Recent discoveries of basal extracellular Rickettsiales have revealed different paths to host dependency in later-evolving lineages. The family Rickettsiaceae, which includes protist-and invertebrate-associated species as well as human pathogens, forms distinct lineages with unique lifestyles and morphological traits. Contrasting other rickettsial human pathogens, the mechanisms for commandeering host glycolysis in Orientia and Rickettsia species remain to be discovered. However, conjugative transposons unique to these species provide critical insights into their intracellular parasitism strategies.

CURRENT OPINION IN MICROBIOLOGY (2023)

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Article Immunology

Distinct Role of TNFR1 and TNFR2 in Protective Immunity Against Orientia tsutsugamushi Infection in Mice

Yuejin Liang et al.

Summary: This study demonstrates the importance of TNF-TNFR signaling in protective immunity against scrub typhus infection. Mice lacking TNFR1 and TNFR2 were highly susceptible to infection, with deficiencies in cellular immunity activation.

FRONTIERS IN IMMUNOLOGY (2022)

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Article Infectious Diseases

Host transcriptomic profiling of CD-1 outbred mice with severe clinical outcomes following infection with Orientia tsutsugamushi

Joseph Thiriot et al.

Summary: This study establishes a valuable mouse model for scrub typhus research and identifies immune biomarkers related to disease severity. The findings contribute to future vaccine studies and provide insights into host susceptibility and disease pathogenesis.

PLOS NEGLECTED TROPICAL DISEASES (2022)

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Article Immunology

CCR7/dendritic cell axis mediates early bacterial dissemination in Orientia tsutsugamushi-infected mice

Yuejin Liang et al.

Summary: Scrub typhus is a life-threatening zoonosis caused by the obligate intracellular bacterium Orientia tsutsugamushi. This study investigates the mechanisms of Ot dissemination from the bite site to visceral organs and the host innate immune response. The study found that neutrophils are the first responders to Ot infection and migrate to the skin for bacterial uptake. However, depletion of neutrophils did not alter bacterial dissemination, and dendritic cells and macrophages were found to transmit Ot from the skin to draining lymph nodes.

FRONTIERS IN IMMUNOLOGY (2022)

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Article Infectious Diseases

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 et al.

Summary: This study evaluated the clinical outcomes and host immune responses of two strains of Orientia tsutsugamushi in a non-human primate model for scrub typhus. The researchers found distinct features in clinical progression and immune response between the two strains, suggesting strain-specific host responses. This study improves our understanding of scrub typhus and provides evidence for future vaccine development.

PLOS NEGLECTED TROPICAL DISEASES (2022)

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Review Microbiology

Orientia tsutsugamushi: The dangerous yet neglected foe from the East

Anwesha Banerjee et al.

Summary: Orientia tsutsugamushi, the causative agent of Scrub typhus, poses challenges in clinical management and research due to its antigenic diversity and non-specific symptoms. The resurgence of OT infections in the Asia-Pacific region has sparked the development of advanced diagnostic techniques and research on vaccine candidates to reduce the burden of the disease.

INTERNATIONAL JOURNAL OF MEDICAL MICROBIOLOGY (2021)

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Review Infectious Diseases

The burden of scrub typhus in India: A systematic review

Emily Devasagayam et al.

Summary: Scrub typhus is a common acute febrile illness in India causing severe morbidity, with a high case-fatality rate. Multiple organ involvement is frequent, increasing the risk of death. Early diagnosis and prompt treatment are crucial to reduce complications and mortality in patients with scrub typhus.

PLOS NEGLECTED TROPICAL DISEASES (2021)

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Article Microbiology

Orientia tsutsugamushi selectively stimulates the C-type lectin receptor Mincle and type 1-skewed proinflammatory immune responses

James Fisher et al.

Summary: Scrub typhus, caused by Orientia tsutsugamushi, is a life-threatening disease that often involves severe lung damage. The dysregulated immune response and the selective activation of Mincle by O. tsutsugamushi may lead to overzealous inflammation and tissue damage. This study provides novel insights into the immune recognition of O. tsutsugamushi and potential pathways for host response to severe infection, shedding light on the innate immune recognition of this bacterium.

PLOS PATHOGENS (2021)

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Article Immunology

CCR2 Deficiency Impairs Ly6Clo and Ly6Chi Monocyte Responses in Orientia tsutsugamushi Infection

Michael Petermann et al.

Summary: Our study investigated the role of CCR2 in a self-healing mouse model of O. tsutsugamushi infection, showing that CCR2 deficiency delayed disease onset, resolved symptoms, and resulted in higher concentrations of bacteria in the lung and impaired clearance. CCR2 drives blood monocytosis and the influx and activation of monocytes into the lung, accelerating bacterial replication and development of pulmonary inflammation.

FRONTIERS IN IMMUNOLOGY (2021)

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Article Infectious Diseases

Comparison of Lethal and Nonlethal Mouse Models of Orientia tsutsugamushi Infection Reveals T-Cell Population-Associated Cytokine Signatures Correlated with Lethality and Protection

Alison Luce-Fedrow et al.

Summary: This study compared host immune responses in lethal and nonlethal murine models of O. tsutsugamushi infection, identifying specific cytokine signatures in the lethal model and predominance of single or double cytokine producers in the nonlethal model.

TROPICAL MEDICINE AND INFECTIOUS DISEASE (2021)

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Article Microbiology

Inflammasome-mediated antagonism of type I interferon enhances Rickettsia pathogenesis

Thomas P. Burke et al.

NATURE MICROBIOLOGY (2020)

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Article Infectious Diseases

Polarized lung inflammation and Tie2/angiopoietin-mediated endothelial dysfunction during severe Orientia tsutsugamushi infection

Brandon Trent et al.

PLOS NEGLECTED TROPICAL DISEASES (2020)

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Editorial Material Multidisciplinary Sciences

Pathogenic T-cells and inflammatory monocytes incite inflammatory storms in severe COVID-19 patients

Yonggang Zhou et al.

NATIONAL SCIENCE REVIEW (2020)

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Article Multidisciplinary Sciences

Dual RNA-seq of Orientia tsutsugamushi informs on host-pathogen interactions for this neglected intracellular human pathogen

Bozena Mika-Gospodorz et al.

NATURE COMMUNICATIONS (2020)

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Review Infectious Diseases

Neuroinflammation associated with scrub typhus and spotted fever group rickettsioses

James Fisher et al.

PLOS NEGLECTED TROPICAL DISEASES (2020)

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Review Microbiology

Scrub Typhus Pathogenesis: Innate Immune Response and Lung Injury During Orientia tsutsugamushi Infection

Brandon Trent et al.

FRONTIERS IN MICROBIOLOGY (2019)

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Review Immunology

Dysregulated Th1 Immune and Vascular Responses in Scrub Typhus Pathogenesis

Lynn Soong

JOURNAL OF IMMUNOLOGY (2018)

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Article Infectious Diseases

Long-read whole genome sequencing and comparative analysis of six strains of the human pathogen Orientia tsutsugamushi

Elizabeth M. Batty et al.

PLOS NEGLECTED TROPICAL DISEASES (2018)

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Article Immunology

A Type I Interferon and IL-10 Induced by Orientia tsutsugamushi Infection Suppresses Antigen-Specific T Cells and Their Memory Responses

Chan-Ki Min et al.

FRONTIERS IN IMMUNOLOGY (2018)

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Article Infectious Diseases

Type 1-skewed neuroinflammation and vascular damage associated with Orientia tsutsugamushi infection in mice

Lynn Soong et al.

PLOS NEGLECTED TROPICAL DISEASES (2017)

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Article Infectious Diseases

CD8+ T cells provide immune protection against murine disseminated endotheliotropic Orientia tsutsugamushi infection

Guang Xu et al.

PLOS NEGLECTED TROPICAL DISEASES (2017)

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Article Infectious Diseases

Increased level and interferon-γ production of circulating natural killer cells in patients with scrub typhus

Seung-Ji Kang et al.

PLOS NEGLECTED TROPICAL DISEASES (2017)

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Review Infectious Diseases

A review of the global epidemiology of scrub typhus

Guang Xu et al.

PLOS NEGLECTED TROPICAL DISEASES (2017)

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Article Infectious Diseases

IL-33-Dependent Endothelial Activation Contributes to Apoptosis and Renal Injury in Orientia tsutsugamushi-Infected Mice

Thomas R. Shelite et al.

PLOS NEGLECTED TROPICAL DISEASES (2016)

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Article Infectious Diseases

Antigenic Relationships among Human Pathogenic Orientia tsutsugamushi Isolates from Thailand

Sarah L. James et al.

PLOS NEGLECTED TROPICAL DISEASES (2016)

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Article Infectious Diseases

An Intradermal Inoculation Mouse Model for Immunological Investigations of Acute Scrub Typhus and Persistent Infection

Lynn Soong et al.

PLOS NEGLECTED TROPICAL DISEASES (2016)

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Article Infectious Diseases

Increased Nucleosomes and Neutrophil Activation Link to Disease Progression in Patients with Scrub Typhus but Not Murine Typhus in Laos

Daniel H. Paris et al.

PLOS NEGLECTED TROPICAL DISEASES (2015)

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Article Multidisciplinary Sciences

Novel Markers to Delineate Murine M1 and M2 Macrophages

Kyle A. Jablonski et al.

PLOS ONE (2015)

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Article Infectious Diseases

Strong Type 1, but Impaired Type 2, Immune Responses Contribute to Orientia tsutsugamushi-Induced Pathology in Mice

Lynn Soong et al.

PLOS NEGLECTED TROPICAL DISEASES (2014)

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Article Infectious Diseases

Dissemination of Orientia tsutsugamushi and Inflammatory Responses in a Murine Model of Scrub Typhus

Christian A. Keller et al.

PLOS NEGLECTED TROPICAL DISEASES (2014)

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Article Infectious Diseases

A Hematogenously Disseminated Orientia tsutsugamsushi-Infected Murine Model of Scrub Typhus

Thomas R. Shelite et al.

PLOS NEGLECTED TROPICAL DISEASES (2014)

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Review Public, Environmental & Occupational Health

Review Article: Unresolved Problems Related to Scrub Typhus: A Seriously Neglected Life-Threatening Disease

Daniel H. Paris et al.

AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE (2013)

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Article Multidisciplinary Sciences

An Intradermal Inoculation Model of Scrub Typhus in Swiss CD-1 Mice Demonstrates More Rapid Dissemination of Virulent Strains of Orientia tsutsugamushi

Piyanate Sunyakumthorn et al.

PLOS ONE (2013)

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Review Immunology

Approaches to vaccines against Orientia tsutsugamushi

Gustavo Valbuena et al.

FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY (2013)

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Article Infectious Diseases

Phenotypic Characterization of Peripheral T Cells and Their Dynamics in Scrub Typhus Patients

Bon-A Cho et al.

PLOS NEGLECTED TROPICAL DISEASES (2012)

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Article Public, Environmental & Occupational Health

First Report of an Orientia tsutsugamushi Type TA716-Related Scrub Typhus Infection in Thailand

Rose McGready et al.

VECTOR-BORNE AND ZOONOTIC DISEASES (2010)

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Review Immunology

Scrub Typhus: The Geographic Distribution of Phenotypic and Genotypic Variants of Orientia tsutsugamushi

Daryl J. Kelly et al.

CLINICAL INFECTIOUS DISEASES (2009)

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Article Microbiology

Orientia tsutsugamushi Bacteremia and Cytokine Levels in Vietnamese Scrub Typhus Patients

Stefanie Kramme et al.

JOURNAL OF CLINICAL MICROBIOLOGY (2009)

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Article Infectious Diseases

Kinetics of inflammatory cytokines in patients with scrub typhus receiving doxycycline treatment

Doo Ryeon Chung et al.

JOURNAL OF INFECTION (2008)

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Article Radiology, Nuclear Medicine & Medical Imaging

Scrub typhus: Clinical, pathologic, and Imaging findings

Yeon Joo Jeong et al.

RADIOGRAPHICS (2007)

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Article Microbiology

Comparative genomic analysis of three strains of Ehrlichia ruminantium reveals an active process of genome size plasticity

R Frutos et al.

JOURNAL OF BACTERIOLOGY (2006)

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Article Public, Environmental & Occupational Health

Activation of cytotoxic lymphocytes in patients with scrub typhus

M De Fost et al.

AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE (2005)

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Article Immunology

Chemokine and cytokine production in susceptible C3H/HeN mice and resistant BALB/c mice during Orientia tsutsugamushi infection

JH Yun et al.

MICROBIOLOGY AND IMMUNOLOGY (2005)

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Article Biochemistry & Molecular Biology

Phylogenomics of the reproductive parasite Wolbachia pipientis wMel:: A streamlined genome overrun by mobile genetic elements

M Wu et al.

PLOS BIOLOGY (2004)

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Article Microbiology

Complete genome sequence of Rickettsia typhi and comparison with sequences of other rickettsiae

MP McLeod et al.

JOURNAL OF BACTERIOLOGY (2004)

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Article Immunology

Differential expression of interferon-γ and interferon-γ-inducing cytokines in Thai patients with scrub typhus or leptospirosis

W Chierakul et al.

CLINICAL IMMUNOLOGY (2004)

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Differential cellular immune responses against Orientia tsutsugamushi Karp and Gilliam strains following acute infection in mice

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