Generation of protective immunity against Orientia tsutsugamushi infection by immunization with a zinc oxide nanoparticle combined with ScaA antigen

Ha, Na Young; Shin, Hyun Mu; Sharma, Prashant; Cho, Hyun Ah; Min, Chan Ki; Kim, Hong Il; Yen, Nguyen Thi Hai; Kang, Jae Seung; Kim, Ik Sang; Choi, Myung Sik; Kim, Young Keun; Cho, Nam Hyuk

doi:10.1186/s12951-016-0229-2

Cited by 35 publications

(37 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TSA56 has four variable domains and these lead to strain-specific antibody responses in patients. TSA47, TSA56, and ScaA have been evaluated as possible vaccine candidates 43,44 . Of the core Ot genes, among those most differentially expressed between Karp and UT176 were scaE, tsa56, and tsa22 (1.40, 3.08, and 3.96 logFC in Karp over UT176, respectively), and differential expression was confirmed by qRT-PCR in an independent infection experiment ( Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

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

et al. 2020

View full text Add to dashboard Cite

Studying emerging or neglected pathogens is often challenging due to insufficient information and absence of genetic tools. Dual RNA-seq provides insights into host-pathogen interactions, and is particularly informative for intracellular organisms. Here we apply dual RNA-seq to Orientia tsutsugamushi (Ot), an obligate intracellular bacterium that causes the vectorborne human disease scrub typhus. Half the Ot genome is composed of repetitive DNA, and there is minimal collinearity in gene order between strains. Integrating RNA-seq, comparative genomics, proteomics, and machine learning to study the transcriptional architecture of Ot, we find evidence for widespread post-transcriptional antisense regulation. Comparing the host response to two clinical isolates, we identify distinct immune response networks for each strain, leading to predictions of relative virulence that are validated in a mouse infection model. Thus, dual RNA-seq can provide insight into the biology and host-pathogen interactions of a poorly characterized and genetically intractable organism such as Ot.

show abstract

Section: Resultsmentioning

confidence: 99%

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

et al. 2020

View full text Add to dashboard Cite

show abstract

“…TSA56 has four variable domains and these lead to strain-specific antibody responses in patients. TSA47, TSA56, and ScaA have been evaluated as possible vaccine candidates 61, 62 . Of the core Ot genes, those most differentially expressed between Karp and UT176 were scaE , tsa56, and tsa22 (1.39, 3.06 and 3.94 logFC in Karp over UT176, respectively).…”

Section: Resultsmentioning

confidence: 99%

Dual RNA-seq provides insight into the biology of the neglected intracellular human pathogenOrientia tsutsugamushi

Mika-Gospodorz

Giengkam

Westermann

et al. 2019

Preprint

View full text Add to dashboard Cite

29Emerging and neglected diseases pose challenges as their biology is frequently poorly understood, and 30 genetic tools often do not exist to manipulate the responsible pathogen. Organism agnostic sequencing 31 technologies offer a promising approach to understand the molecular processes underlying these diseases. 32Here we apply dual RNA-seq to Orientia tsutsugamushi (Ot), an obligate intracellular bacterium and the 33 causative agent of the vector-borne human disease scrub typhus. Half the Ot genome is composed of 34 repetitive DNA, and there is minimal collinearity in gene order between strains. Integrating RNA-seq, 35 comparative genomics, proteomics, and machine learning, we investigated the transcriptional architecture 36 of Ot, including operon structure and non-coding RNAs, and found evidence for wide-spread post-37 transcriptional antisense regulation. We compared the host response to two clinical isolates and identified 38 distinct immune response networks that are up-regulated in response to each strain, leading to predictions 39 of relative virulence which were confirmed in a mouse infection model. Thus, dual RNA-seq can provide 40 insight into the biology and host-pathogen interactions of a poorly characterized and genetically 41 intractable organism such as Ot. 42 43 Keywords: neglected and emerging pathogens, intracellular bacteria, dual RNA-seq, transcriptomics, 44 host-pathogen cell biology, bacterial virulence, antisense transcription. 45 4 Main Text 46 48 serious pathogens, whilst human population growth, globalization and increased travel have contributed 49 to the emergence of new pathogens and changing patterns of infectious disease. The biology of neglected 50 and emerging pathogens is often poorly understood, but is essential to developing therapeutic and 51 preventative strategies. Obligate intracellular pathogens present additional challenges, as many cause 52 diseases that are difficult to diagnose and are difficult to manipulate experimentally. 53 54 Obligate intracellular bacteria include the Rickettsiales, an order which includes the arthropod and 55 nematode symbiont Wolbachia as well as a number of human and veterinary pathogens. Orientia 56 tsutsugamushi (Ot, Class Alphaproteobacteria, Order Rickettsiales, Family Rickettsiaceae) causes the 57 mite-borne human disease scrub typhus, a leading cause of severe febrile illness in the Asia Pacific region 1 , 58 home to roughly two thirds of the world's population. Locally acquired cases in the Middle East and Latin 59America suggest that this disease may be more widespread than previously appreciated 2,3 . Under-60 recognition and under-reporting are a major problem in scrub typhus because unambiguous diagnosis is 61 difficult, and awareness is low amongst many clinicians. Symptoms are non-specific and include 62 headache, fever, rash, and lymphadenopathy beginning 7-14 days after inoculation via a feeding larval 63 stage mite. If untreated, this can progress to cause multiple organ failure and death. In the mite vector Ot 64 colonizes...

show abstract

“…Even though early diagnosis followed by appropriate antibiotic therapy can efficiently control the febrile illness, several problems, including relatively high mortality in untreated patients or after delayed diagnosis ( 13 ), potential antibiotic resistance ( 14 ), recurrent infection in highly endemic areas ( 15 ), and growing urbanization primarily due to ecological changes of mite vectors ( 16 ), pose challenges in the endemic area. Moreover, an effective vaccine for human infection is not yet available despite continuous efforts since the 1940s ( 17 , 18 ).…”

Section: Introductionmentioning

confidence: 99%

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

Min

Kim

et al. 2018

Front. Immunol.

Self Cite

View full text Add to dashboard Cite

Despite the various roles of type I interferon (type I IFN) responses during bacterial infection, its specific effects in vivo have been poorly characterized in scrub typhus caused by Orientia tsutsugamushi infection. Here, we show that type I IFNs are primarily induced via intracellular nucleic acids sensors, including RIG-I/MAVS and cGAS/STING pathways, during O. tsutsugamushi invasion. However, type I IFN signaling did not significantly affect pathogenesis, mortality, or bacterial burden during primary infection in vivo, when assessed in a mice model lacking a receptor for type I IFNs (IFNAR KO). Rather, it significantly impaired the induction of antigen-specific T cells and reduced memory T cell responses. IFNAR KO mice that recovered from primary infection showed stronger antigen-specific T cell responses, especially Th1, and more efficiently controlled bacteremia during secondary infection than wild type mice. Enhanced IL-10 expression by macrophages in the presence of type I IFN signaling might play a significant role in the suppression of antigen-specific T cell responses as neutralization or knock-out (KO) of IL-10 increased T cell responses in vitro. Therefore, induction of the type I IFN/IL-10 axis by O. tsutsugamushi infection might play a significant role in the suppression of T cell responses and contribute to the short longevity of cell-mediated immunity, often observed in scrub typhus patients.

show abstract

Generation of protective immunity against Orientia tsutsugamushi infection by immunization with a zinc oxide nanoparticle combined with ScaA antigen

Cited by 35 publications

References 47 publications

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

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

Dual RNA-seq provides insight into the biology of the neglected intracellular human pathogenOrientia tsutsugamushi

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

Contact Info

Product

Resources

About