Neutrophils Play an Important Role in Protective Immunity against Coxiella burnetii Infection

Elliott, Alexandra; Schoenlaub, Laura; Freches, Danielle; Mitchell, William J.; Zhang, Guoquan

doi:10.1128/iai.00042-15

Cited by 18 publications

(20 citation statements)

References 32 publications

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“…***, P Ͻ 0.001; ****, P Ͻ 0.0001. measured by quantitative real-time PCR. In addition, recent studies (13,14,25,(27)(28)(29)(30) demonstrated that both C. burnetii i.p. and respiratory infections cause similar systemic infections in mice and induce a significant and comparable splenomegaly at different time points postinfection.…”

Section: Figmentioning

confidence: 99%

Both Major Histocompatibility Complex Class I (MHC-I) and MHC-II Molecules Are Required, while MHC-I Appears To Play a Critical Role in Host Defense against Primary Coxiella burnetii Infection

et al. 2018

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To understand the role of class I major histocompatibility complex (MHC-I) and class II MHC (MHC-II) antigen presentation pathways in host defense against infection, we examined whether MHC-I or MHC-II deficiency in mice would significantly influence their susceptibility to virulent Nine Mile phase I (NMI) infection. The results indicate that NMI infection induced more severe disease in both MHC-I-deficient and MHC-II-deficient mice than in wild-type (WT) mice, while only MHC-I-deficient mice developed a severe persistent infection and were unable to control bacterial replication. These results suggest that both MHC-I-restricted CD8 T cells and MHC-II-restricted CD4 T cells contribute to host defense against primary infection, while MHC-I-restricted CD8 T cells appear to play a more critical role in controlling bacterial replication. Additionally, although NMI infection induced more severe disease in TAP1-deficient mice than in their WT counterparts, TAP1 deficiency in mice did not significantly influence their ability to eliminate This suggests that antigen presentation to CD8 T cells by the MHC-I classical pathway may depend only partially on TAP1. Furthermore, granzyme B deficiency in mice did not significantly alter their susceptibility to infection, but perforin-deficient mice were unable to control host inflammatory responses during primary infection. These results suggest that perforin, but not granzyme B, is required for antigen-specific cytotoxic CD8 T cells to control primary infection.

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Section: Figmentioning

confidence: 99%

Both Major Histocompatibility Complex Class I (MHC-I) and MHC-II Molecules Are Required, while MHC-I Appears To Play a Critical Role in Host Defense against Primary Coxiella burnetii Infection

et al. 2018

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“…This finding suggests that ART has beneficial effects on the immune system beyond those measured with CD4 cell count. Neutrophils play a key part in the innate immune response to bacterial infection 11 . Known as the hallmark of inflammation, neutrophils are the first of the white blood cells to migrate towards a site of bacterial infection to begin killing the invading microbes 12 .…”

Section: Introductionmentioning

confidence: 99%

Effect of immediate initiation of antiretroviral therapy on risk of severe bacterial infections in HIV-positive people with CD4 cell counts of more than 500 cells per μL: secondary outcome results from a randomised controlled trial

et al. 2017

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SummaryBackgroundThe effects of antiretroviral therapy on risk of severe bacterial infections in people with high CD4 cell counts have not been well described. In this study, we aimed to quantify the effects of immediate versus deferred ART on the risk of severe bacterial infection in people with high CD4 cell counts in a preplanned analysis of the START trial.MethodsThe START trial was a randomised controlled trial in ART-naive HIV-positive patients with CD4 cell count of more than 500 cells per μL assigned to immediate ART or deferral until their CD4 cell counts were lower than 350 cells per μL. We used Cox proportional hazards regression to model time to severe bacterial infection, which was defined as a composite endpoint of bacterial pneumonia (confirmed by the endpoint review committee), pulmonary or extrapulmonary tuberculosis, or any bacterial infectious disorder of grade 4 severity, that required unscheduled hospital admissions, or caused death. This study is registered with ClinicalTrials.gov, number NCT00867048.FindingsPatients were recruited from April 15, 2009, to Dec 23, 2013. The data cutoff for follow-up was May 26, 2015. Of 4685 HIV-positive people enrolled, 120 had severe bacterial infections (immediate-initiation group n=34, deferred-initiation group n=86; median 2·8 years of follow-up). Immediate ART was associated with a reduced risk of severe bacterial infection compared with deferred ART (hazard ratio [HR] 0·39, 95% CI 0·26–0·57, p<0·0001). In the immediate-initiation group, average neutrophil count over follow-up was 321 cells per μL higher, and average CD4 cell count 194 cells per μL higher than the deferred-initiation group (p<0·0001). In univariable analysis, higher time-updated CD4 cell count (0·78, 0·71–0·85, p=0·0001) was associated with reduced risk of severe bacterial infection. Time-updated neutrophil count was not associated with severe bacterial infection. After adjustment for time-updated factors in multivariable analysis, particularly the CD4 cell count, the HR for immediate-initiation group moved closer to 1 (HR 0·84, 0·50–1·41, p=0·52). These results were consistent when subgroups of the severe bacterial infection composite were analysed separately.InterpretationImmediate ART reduces the risk of several severe bacterial infections in HIV-positive people with high CD4 cell count. This is partly explained by ART-induced increases in CD4 cell count, but not by increases in neutrophil count.FundingNational Institute of Allergy and Infectious Diseases National Institutes of Health, Agence Nationale de Recherches sur le SIDA et les Hépatites Virales, Bundesministerium für Bildung und Forschung, European AIDS Treatment Network, Australian National Health and Medical Research Council, UK National Institute for Health Research and Medical Research Council, Danish National Research Foundation.

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“…Dendritic cells and monocytes may be the target cells of Orientia tsutsugamushi that can cause vasculitis and reticuloendothelial cell proliferation [37,38], which may be cause skin rash and lymphadenopathy. In contrast, C. burnetti can invade the monocytes and macrophages, leading to granuloma formation [39][40][41].Based on the above-mentioned ndings, we emphasize the meticulous physical examination to nd the characteristic presentation when a febrile patient comes.…”

Section: Discussionmentioning

confidence: 88%

Acute Q Fever Diagnosed by Metagenomic Next-generation Sequencing and Clinically Compared With Scrub Typhus

Liu¹,

Lin²,

Zhu³

et al. 2020

Preprint

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Background: C. burnetti, the causative agent of Q fever, is considered a potential threat as a biological weapon because of highly infectious and pathogenic. There was an outbreak of Q fever in Zhuhai, P.R. China between December, 2018 and March 2019, although Zhuhai was not the endemic area of Q fever. 46 patients can be detected C. burnetti by metagenomic next-generation sequencing (mNGS). There are many similarities between acute Q fever and scrub typhus in clinical manifestations. Methods: We analyze the differences of clinical manifestations and serological between 46 patients with acute Q fever and 100 patients with scrub typhus. The general information of patients including gender, age, basic disease, days from disease onset and clinical manifestations were evaluated. Results: Their mean age of acute Q fever was 43.6±11.8 (ranging from 32 to 55 years old), younger than scrub typhus patients (53.9±12.7, ranging from 41 to 67 years old) (P<0.001). Males are more susceptible to C. burnetti. There were 45 males (97.8%) in acute Q fever patients and 59 males (59.0%) in scrub typhus patients (P<0.001). Compared with scrub typhus, patients with acute Q fever are more prone to present sore throat (P=0.003), abnormal liver function (P<0.001) and elevated levels of procalcitonin (P<0.001). Meanwhile, skin rash (P<0.001), eschar (P<0.001), lymphadenopathy (P<0.001), leukocytosis (P<0.001), thrombocytopenia (P=0.003), eosinophils reducing or disappearing (P=0.002) and pulmonary involvement on chest imaging (P=0.003) were more common in scrub typhus. There was significant difference between the two groups (P<0.001). Days from minocycline treatment to defervescence in acute Q fever (1.82±1.357, ranging from 0.5 to 3.2 days) were shorter than scrub typhus (2.85±2.801, ranging from 0.0 to 5.7 days) (P=0.008). Conclusions: mNGS is helpful to early diagnosis of acute Q fever. Sex, age, serologic test and physical examination are important in the differentiation of acute Q fever from scrub typhus in Zhuhai, China.

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Neutrophils Play an Important Role in Protective Immunity against Coxiella burnetii Infection

Cited by 18 publications

References 32 publications

Both Major Histocompatibility Complex Class I (MHC-I) and MHC-II Molecules Are Required, while MHC-I Appears To Play a Critical Role in Host Defense against Primary Coxiella burnetii Infection

Both Major Histocompatibility Complex Class I (MHC-I) and MHC-II Molecules Are Required, while MHC-I Appears To Play a Critical Role in Host Defense against Primary Coxiella burnetii Infection

Effect of immediate initiation of antiretroviral therapy on risk of severe bacterial infections in HIV-positive people with CD4 cell counts of more than 500 cells per μL: secondary outcome results from a randomised controlled trial

Acute Q Fever Diagnosed by Metagenomic Next-generation Sequencing and Clinically Compared With Scrub Typhus

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