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

Kang, Seung-Ji; Jin, Hye-Mi; Cho, Young-Nan; Kim, Seong Eun; Kim, Uh Jin; Park, Kyung‐Hwa; Jang, Hee-Chang; Jung, Sook-In; Kee, Seung‐Jung; Park, Yong-Wook

doi:10.1371/journal.pntd.0005815

Cited by 19 publications

(23 citation statements)

References 48 publications

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“…Whereas at 24 h HLA-ABC and ␤2M chain amounts were slightly lower in O. tsutsugamushi-infected cells than in uninfected cells, by 72 h they had significantly decreased by 74% and 65%, respectively. Gamma interferon (IFN-␥), a cytokine whose levels are elevated during O. tsutsugamushi infection of humans and mice, can stimulate expression of MHC-I components (1, [34][35][36][37][38]. Even in the presence of IFN-␥, the bacterium pronouncedly reduced the cellular levels of HLA-ABC and ␤2M.…”

Section: Resultsmentioning

confidence: 99%

The Obligate Intracellular Bacterium Orientia tsutsugamushi Targets NLRC5 To Modulate the Major Histocompatibility Complex Class I Pathway

et al. 2019

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Orientia tsutsugamushiis an obligate intracellular bacterium that infects mononuclear and endothelial cells to cause the emerging global health threat scrub typhus. The ability ofO. tsutsugamushito survive in monocytes facilitates bacterial dissemination to endothelial cells, which can subsequently lead to several potentially fatal sequelae. As a strict intracellular pathogen that lives in the cytoplasm of host cells,O. tsutsugamushihas evolved to counter adaptive immunity. How the pathogen does so and the outcome of this strategy in monocytes versus endothelial cells are poorly understood. This report demonstrates thatO. tsutsugamushireduces cellular levels of NOD-, LRR-, and CARD-containing 5 (NLRC5), a recently identified specific transactivator of major histocompatibility complex class I (MHC-I) component gene expression, to inhibit MHC-I biosynthesis. Importantly, the efficacy of this approach varies with the host cell type infected. In nonprofessional antigen-presenting HeLa and primary human aortic endothelial cells, theO. tsutsugamushi-mediated reduction of NLRC5 results in lowered MHC-I component transcription and, consequently, lower total and/or surface MHC-I levels throughout 72 h of infection. However, in infected THP-1 monocytes, which are professional antigen-presenting cells, the reductions in NLRC5 and MHC-I observed during the first 24 h reverse thereafter.O. tsutsugamushiis the first example of a microbe that targets NLRC5 to modulate the MHC-I pathway. The differential ability ofO. tsutsugamushito modulate this pathway in nonprofessional versus professional antigen-presenting cells could influence morbidity and mortality from scrub typhus.

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Section: Resultsmentioning

confidence: 99%

The Obligate Intracellular Bacterium Orientia tsutsugamushi Targets NLRC5 To Modulate the Major Histocompatibility Complex Class I Pathway

et al. 2019

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“…Expression of CD11c and CD69 on this peripheral cell subset is very intriguing, as these two markers are normally detected to a higher degree in tissue-resident NK cells (54,55). In addition, it has been shown that CD69 + NK cells expressed IFN-γ to a higher degree than CD69 − NK cells (56). A higher frequency of activated NK cells with a pro-inflammatory phenotype in adults with newly diagnosed T1D might reflect the ongoing inflammatory process, as this alteration was not observed in samples from patients with L-T1D.…”

Section: Discussionmentioning

confidence: 99%

Mass Cytometry Studies of Patients With Autoimmune Endocrine Diseases Reveal Distinct Disease-Specific Alterations in Immune Cell Subsets

et al. 2020

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Although there is evidence that autoimmune diseases share similar immunogenetic mechanisms, studies comparing peripheral CD45 + cells from patients with autoimmune endocrine diseases in parallel are limited. In this study, we applied high-dimensional single-cell mass cytometry to phenotypically characterize PBMC from patients with new-onset (N-T1D) and long-standing type 1 diabetes, Hashimoto's thyroiditis (HT), Graves' disease and autoimmune Addison's disease (AD), as well as healthy controls. The frequency of CD20 lo CD27 hi CD38 hi HLA-DR int plasmablasts, CD86 + CD14 lo CD16 + non-classical monocytes and two subsets of CD56 dim HLA-DR + IFN-γ + NK cells were increased in patients with HT. Subsets of CD56 dim CD69 + HLA-DR − NK cells and CD8 + TEMRA cells, both expressing IFN-γ, were expanded and reduced, respectively, in the N-T1D group. In addition, patients with AD were characterized by an increased percentage of central memory CD8 + T cells that expressed CCR4, GATA3, and IL-2. We demonstrate that patients with N-T1D, HT, and AD had altered frequencies of distinct subsets within antigen-presenting and cytotoxic cell lineages. Previously unreported alterations of specific cell subsets were identified in samples from patients with HT and AD. Our study might contribute to a better understanding of shared and diverging immunological features between autoimmune endocrine diseases.

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“…Consistent with this result, dominance of Th1-biased immune responses, as represented by elevated IFN-γ ( Figure 3 ), has also been observed in scrub typhus patients. 36 , 37 In summary, cellular immunity mediated by antigen-specific T cells may have a significant role in the eradication of bacterial pathogens from infected patients. ScaA- or TSA56-specific T cells, however, rapidly declined at 1 year after infection and were barely detectable at 2 years after recovery.…”

Section: Discussionmentioning

confidence: 99%

Longevity of antibody and T-cell responses against outer membrane antigens of Orientia tsutsugamushi in scrub typhus patients

Kim

Min

et al. 2017

Emerging Microbes & Infections

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Scrub typhus, caused by Orientia tsutsugamushi infection, has been a serious public health issue in the Asia-Pacific region, with rising incidence and sporadic outbreaks. However, human protective immunity against specific antigens has been poorly characterized for this bacterium. In addition, immunity produced in early vaccine trials or even after natural infections, did not last long and had poor cross-reactivity among various genotypes. Here, we systematically investigated the kinetics and magnitude of specific adaptive immunity against two membrane antigens, 56 kDa type-specific antigen (TSA56) and surface cell antigen A (ScaA), that are involved in bacterial adhesion and invasion of the host in 64 recovered scrub typhus patients. Antibody responses to the bacterial antigens in patients were generally short-lived and waned to baseline levels 2 years after recovery. The anti-TSA56 IgG responses were predominantly composed of the IgG1 and IgG3 subclasses and persisted for up to 1 year after recovery, whereas IgG specific to ScaA primarily consisted of more transient IgG1, with limited responses by other subclasses. Cellular immunity, including CD4 and CD8 T-cells specific to membrane antigens, also rapidly declined from 1 year after infection, as measured by enzyme-linked immunospot (ELISPOT) assays and flow cytometry. The short longevity of antigen-specific adaptive immunity might be attributable to limited memory responses, as observed in earlier vaccine studies using whole bacterial antigens. Finally, we identified HLA-A*0201-restricted and highly conserved CD8 T-cell epitopes in the TSA56 antigen, which may be valuable tools for assessing cellular immunity against O. tsutsugamushi and developing an effective scrub typhus vaccine.

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

Cited by 19 publications

References 48 publications

The Obligate Intracellular Bacterium Orientia tsutsugamushi Targets NLRC5 To Modulate the Major Histocompatibility Complex Class I Pathway

The Obligate Intracellular Bacterium Orientia tsutsugamushi Targets NLRC5 To Modulate the Major Histocompatibility Complex Class I Pathway

Mass Cytometry Studies of Patients With Autoimmune Endocrine Diseases Reveal Distinct Disease-Specific Alterations in Immune Cell Subsets

Longevity of antibody and T-cell responses against outer membrane antigens of Orientia tsutsugamushi in scrub typhus patients

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