Detection of <i>Orientia</i> spp. Bacteria in Field-Collected Free-Living <i>Eutrombicula</i> Chigger Mites, United States

Chen, Kaiying; Travanty, Nicholas V.; Garshong, Reuben; Crossley, D. A.; Wasserberg, Gideon; Apperson, Charles S.; Roe, R. Michael; Ponnusamy, Loganathan

doi:10.3201/eid2908.230528

Cited by 12 publications

(3 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recent studies have identified scrub typhus in areas previously believed to be free of this disease, including South America and Africa [5,6]. In 2023, the molecular detection of Orientia species was reported, for the first time, in free-living Eutrombicula chiggers collected in North Carolina [7], which highlights the concerning potential of human illness related to Ot infection in the United States. At present, no effective vaccines are available for scrub typhus, partly due to the antigenic diversity among various Ot strains and undefined roles of host immune responses in controlling or promoting the infection [8,9].…”

Section: Introductionmentioning

confidence: 99%

Lack of the IFN-γ signal leads to lethalOrientia tsutsugamushiinfection in mice with skin eschar lesions

Liang,

Wang,

Sun

et al. 2024

Preprint

View full text Add to dashboard Cite

Scrub typhus is an acute febrile disease due toOrientia tsutsugamushi(Ot) infection and can be life-threatening with organ failure, hemorrhage, and fatality. Yet, little is known as to how the host reacts toOtbacteria at early stages of infection; no reports have addressed the functional roles of type I versus type II interferon (IFN) responses in scrub typhus. In this study, we used comprehensive intradermal (i.d.) inoculation models and two clinically predominantOtstrains (Karp and Gilliam) to uncover early immune events. Karp infection induced sequential expression ofIfnbandIfngin inflamed skin and draining lymph nodes at days 1 and 3 post-infection. Using doubleIfnar1-/-Ifngr1-/-andStat1-/-mice, we found that deficiency in IFN/STAT1 signaling resulted in lethal infection with profound pathology and skin eschar lesions, that resembled to human scrub typhus. Further analyses demonstrated that deficiency in IFN-γ, but not IFN-I, resulted in impaired NK cell and macrophage activation and uncontrolled bacterial growth and dissemination, leading to metabolic dysregulation, excessive inflammatory cell infiltration, and exacerbated tissue damage. NK cells were found to be the major cellular source of early IFN-γ, contributing to the initialOtcontrol. In vitro studies with dendritic cell cultures revealed a superior antibacterial effect offered by IFN-γ than IFN-β. Comparative in vivo studies with Karp- and Gilliam-infection revealed a crucial role of IFN-γ signaling in protection against progression of eschar lesions andOtinfection lethality. Additionally, our i.d. mouse models of lethal infection with eschar lesions are promising tools for immunological study and vaccine development for scrub typhus.SummaryScrub typhus can lead to severe complications and even fatality if not treated properly; however, the early host immune responses toOtbacterium infection remain unclear. This study focused on the functional roles of IFNs in i.d. inoculation mouse models of scrub typhus. We found that mice lacking IFN receptors were highly susceptible toOtinfection, which resulted in severe pathology and skin eschar lesions that resembled to human scrub typhus. Further investigation revealed that the lack of IFN-γ, but not IFN-I, resulted in dysregulated innate immune responses, leading to uncontrolled bacterial burdens and tissue damage. Using IFN-γ reporter mice and neutralizing antibody treatment, we confirmed that NK cells were the major source of early IFN-γ, and thus played a key role in controllingOtdissemination. Moreover, our comparative studies with twoOtstrains revealed bacterium strain- and dose-dependent eschar formation and disease severity. In conclusion, our study highlights the crucial role of IFN-γ signaling in ensuring host protection againstOtinfection. Our mouse models resemble skin eschar lesions and lethal infections observed in human disease, offering potential for future immunological studies on scrub typhus.

show abstract

Section: Introductionmentioning

confidence: 99%

Lack of the IFN-γ signal leads to lethalOrientia tsutsugamushiinfection in mice with skin eschar lesions

Liang,

Wang,

Sun

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…On the opposite side of the world Orientia tsutsugamuschi causes >1 million cases a year of scrub thyphus transmitted by chiggers, which is found primarily in southeast Asia but has an expanding territory and where the emergence of antibiotic-resistant strains is a significant concern ( Luce-Fedrow et al., 2018 ). Recently, O. tsutsugamuschi was found in chiggers in North Carolina, indicating their presence in the USA, although the spread of disease has not occurred to date ( Chen et al., 2023 ). The rise of infections and expansion of vector territories for these obligate intracellular bacteria are making them a rising public health concern.…”

Section: Introductionmentioning

confidence: 99%

Vaccine development: obligate intracellular bacteria new tools, old pathogens: the current state of vaccines against obligate intracellular bacteria

van Schaik,

Fratzke,

Gregory

et al. 2024

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

Obligate intracellular bacteria have remained those for which effective vaccines are unavailable, mostly because protection does not solely rely on an antibody response. Effective antibody-based vaccines, however, have been developed against extracellular bacteria pathogens or toxins. Additionally, obligate intracellular bacteria have evolved many mechanisms to subvert the immune response, making vaccine development complex. Much of what we know about protective immunity for these pathogens has been determined using infection-resolved cases and animal models that mimic disease. These studies have laid the groundwork for antigen discovery, which, combined with recent advances in vaccinology, should allow for the development of safe and efficacious vaccines. Successful vaccines against obligate intracellular bacteria should elicit potent T cell memory responses, in addition to humoral responses. Furthermore, they ought to be designed to specifically induce strong cytotoxic CD8+ T cell responses for protective immunity. This review will describe what we know about the potentially protective immune responses to this group of bacteria. Additionally, we will argue that the novel delivery platforms used during the Sars-CoV-2 pandemic should be excellent candidates to produce protective immunity once antigens are discovered. We will then look more specifically into the vaccine development for Rickettsiaceae, Coxiella burnetti, and Anaplasmataceae from infancy until today. We have not included Chlamydia trachomatis in this review because of the many vaccine related reviews that have been written in recent years.

show abstract

“…8,9 Locally acquired cases in Africa, the Middle East, and South America and detection of Orientia species in mites in the United States signify scrub typhus as a globally emerging health threat. 10-17 O. tsutsugamushi infects leukocytes at the mite feeding site and disseminates to invade endothelial cells of multiple organs. 18,19 Acute scrub typhus symptoms are non-specific and include fever, rash, headache, and lymphadenopathy.…”

Section: Introductionmentioning

confidence: 99%

Orientia tsutsugamushiAnk5 directs ubiquitination and proteasomal degradation of NLRC5 to inhibit major histocompatibility complex class I expression

Adcox,

Hunt,

Rodino

et al. 2023

Preprint

View full text Add to dashboard Cite

How intracellular bacteria subvert the major histocompatibility complex (MHC) class I pathway is poorly understood. Here, we show that the obligate intracellular bacteriumOrientia tsutsugamushiuses its effector protein, Ank5, to orchestrate proteasomal degradation of the MHC class I gene transactivator, NLRC5. Ank5 uses a tyrosine in its fourth ankyrin repeat to bind the NLRC5 N-terminus while its F-box directs host SCF complex ubiquitination of K1194 in the leucine-rich repeat region that dictates NLRC5 susceptibility toOrientia- and Ank5-mediated degradation. The ability ofO. tsutsugamushistrains to degrade NLRC5 correlates withank5genomic carriage. Ectopically expressed Ank5 that can bind but not degrade NLRC5 protects the transactivator duringOrientiainfection. Thus, Ank5 is an immunoevasin that uses its bipartite architecture to rid host cells of NLRC5 and MHC class I molecules. This study offers insight into how intracellular pathogens can impair MHC class I expression to benefit their survival.

show abstract

Detection of Orientia spp. Bacteria in Field-Collected Free-Living Eutrombicula Chigger Mites, United States

Cited by 12 publications

References 12 publications

Lack of the IFN-γ signal leads to lethalOrientia tsutsugamushiinfection in mice with skin eschar lesions

Lack of the IFN-γ signal leads to lethalOrientia tsutsugamushiinfection in mice with skin eschar lesions

Vaccine development: obligate intracellular bacteria new tools, old pathogens: the current state of vaccines against obligate intracellular bacteria

Orientia tsutsugamushiAnk5 directs ubiquitination and proteasomal degradation of NLRC5 to inhibit major histocompatibility complex class I expression

Contact Info

Product

Resources

About