Journal of Infectious Diseases

No abstract text is available yet for this article.

BACKGROUND: Liver kinase B1 (LKB1) has been studied extensively as a tumor suppressor gene (Stk11) in the context of cancer. We hypothesized that myeloid LKB1 plays a role in innate immunity during pneumonia. METHODS: Mice deficient for LKB1 in myeloid cells (LysM-cre x Stk11fl/fl ) or neutrophils (Mrp8-cre x Stk11fl/fl) were infected with Klebsiellapneumoniae via the airways. LysM-cre x Stk11fl/fl mice were also intranasally challenged with lipopolysaccharide (LPS)...

BACKGROUND: Controlled human hookworm infections could significantly contribute to the development of a hookworm vaccine. However, current models are hampered by low and unstable egg output, reducing generalizability and increasing sample sizes. This study aims to investigate the safety, tolerability and egg output of repeated exposure to hookworm larvae. METHODS: Twenty-four healthy volunteers were randomized double blind to one, two or three doses of 50 Necatoramericanus L3 larvae at 2-week intervals...

BACKGROUND: Base excision repair (BER), consisting mostly of lesion-specific DNA glycosylases and apurinic/apyrimidinic (AP) endonucleases, is one of the most important DNA repair mechanisms for repair of single nucleobase lesions generated by reactive oxygen and nitrogen species as part of an immune response against bacterial infections. However, few studies have addressed the contribution of BER to bacterial virulence and Listeria monocytogenes BER has thus far remained completely uncharacterized...

BACKGROUND: Persons living with HIV (PWH) with resistance to antiretroviral therapy (ART) are vulnerable to adverse HIV-related health outcomes and can contribute to transmission of HIV drug resistance (HIVDR) when non-virally suppressed. The degree to which HIVDR contributes to disease burden in Florida -the US state with the highest HIV incidence- is unknown. METHODS: We explored sociodemographic, ecological, and spatial-temporal associations of HIVDR. HIV-1 sequences (n=34,447) collected during 2012-2017 were obtained from the Florida Department of Health...

BACKGROUND: Relations between different measures of HIV-related immunosuppression and chronic kidney disease (CKD) remain unknown. METHODS: Immunosuppression measures included baseline, current, time-lagged and nadir CD4, years and percentage of follow-up (%FU) with CD4<200, and CD4 recovery. CKD: confirmed estimated glomerular filtration rate <60mL/min/1.73m2. RESULTS: Of 33,791 persons 2,226 developed CKD. Univariably, all immunosuppression measures predicted CKD...

BACKGROUND: Combination antiretroviral therapy (cART) during pregnancy prevents vertical transmission, but many antiretrovirals cross the placenta and several can affect mitochondria. Exposure to maternal HIV and/or cART could have long-term effects on children HIV-exposed uninfected (CHEU). Our objective was to compare blood mitochondrial DNA (mtDNA) content in CHEU and children HIV-unexposed uninfected (CHUU), at birth and in early life. METHODS: Birth and early life (0-3y) whole blood mtDNA content was compared cross-sectionally between CHEU and CHUU children...

In Indonesia, BCG protection against M. tuberculosis infection decreased with increasing exposure to the pathogen. We aimed to validate these findings in Africa. Poisson regression was used to estimate BCG protection, stratified by exposure using an exposure score, against ELISPOT conversion at 3 months in 220 Gambian case contacts. While the interaction between BCG and exposure was not significant (p=0.13), BCG protection was strongest in the lowest exposure tertile (RR, 0.35 [95% CI,0.15-0.82]; P=0.02), and the RRs for the middle and highest tertile were 0...

Measles virus (MeV) binds, infects and kills CD150+ memory T-cells, leading to "immune amnesia". Whether MeV targets innate, memory-like T-cells is unknown. We demonstrate that human peripheral blood and hepatic MAIT and iNKT cells express surprisingly high levels of CD150, more than any other lymphocyte subsets, including central and effector memory T-cells. Furthermore, exposing MAIT cells to MeV results in their efficient infection and rapid apoptosis. This constitutes the first report of direct MAIT cell infection by a viral pathogen...

Tick-borne encephalitis virus (TBEV) is a single-stranded, positive-sense RNA virus in the family Flaviviridae that is endemic in parts of Europe and Asia and can cause meningitis or encephalitis. Due to the disease severity, TBEV requires handling under heightened biosafety measures. The establishment and validation of inactivation procedures is a prerequisite for downstream analyses and management of occupational exposure. Therefore, different procedures for TBEV inactivation were tested. Our results suggest that TBEV is susceptible to inactivation by heat, acidic pH, different concentrations of alcohol, formaldehyde or detergents and exposure to UV irradiation, which may depend on sample size and composition...

Cytomegalovirus is a major infectious cause of mortality and morbidity following transplantation. We have previously demonstrated that the tissue-associated adaptive Vδ2neg γδ T-cells are key effectors responding to CMV and associated to recovery, contrasting with their innate-like circulating counterparts, the Vγ9posVδ2pos T-cells that respond to phosphoantigens but not to CMV. A third additional Vγ9negVδ2pos subgroup with adaptive functions has been recently described in adults. Here, we demonstrate that these Vγ9negVδ2pos T-cells are also components of the CMV immune response while presenting with distinct characteristics from Vδ2neg γδT-cells...

No abstract text is available yet for this article.

Our current knowledge of the clinical burden, biology, and transmission of Plasmodium malariae is extremely scarce. To start addressing some of those questions, we experimentally infected Anopheles gambiae mosquitoes with fresh P. malariae isolates obtained from asymptomatic individuals in Lambaréné, Gabon. The proportion of mosquitoes infected via direct membrane feeding assay with either P. malariae mono-infections (16%; 19/121) or co-infections (28%; 31/112) was higher after serum replacement compared to parallel groups without serum replacement (4%, 4/102; and 4%, 2/45; p<0...

BACKGROUND: China implemented the globally synchronized switch from trivalent oral poliovirus vaccine (tOPV) to bivalent OPV (bOPV) and introduced one dose of inactivated poliovirus vaccine (IPV) on May 1st 2016. We assessed the impact of the switch on the immunity level against poliovirus, especially type 2. METHODS: Children born between 2014 and 2017, who were brought to the hospitals in Urumqi city, Xinjiang Province in 2017 were enrolled and blood samples were collected to test for antibody titres against poliovirus...

BACKGROUND: Understanding immunogenicity and safety of monovalent type-2 oral polio vaccine (mOPV2) in inactivated polio vaccine (IPV)-immunized children is of major importance to inform global policy to control circulating vaccine-derived poliovirus (cVDPV) outbreaks. METHODS: In this open-label, phase 4 study (NCT02582255) in 100 IPV-vaccinated Lithuanian 1-5-year-olds we measured humoral and intestinal type-2 polio neutralizing antibodies before and 28 days after one or two mOPV2 doses given 28 days apart, and stool viral shedding after each dose...

BACKGROUND AND AIMS: In patients undergoing orthotopic liver transplant (OLT), immunosuppressive (IS) treatment is mandatory and infections are leading causes of morbidity/mortality. Thus, it is essential to understand the functionality of cell-mediated immunity after OLT. The aim of the study was to identify changes in T cell phenotype and polyfunctionality in HIV+ and HIV- patients treated with IS after OLT. METHODS: We studied peripheral blood mononuclear cells from 108 subjects divided in 4 groups of 27: HIV+ transplanted patients; HIV- transplanted patients; HIV+ non-transplanted patients; healthy subjects...

Understanding in-utero transfer of antiretrovirals is critical for interpreting safety. Hair levels measure cumulative exposure. We measured tenofovir concentrations in hair at delivery among women living with HIV receiving tenofovir-disoproxil-fumarate-based treatment and their infants using liquid chromatography/tandem mass-spectrometry. Among 103 mother-infant pairs, the mean log10-ratio of infant-to-maternal tenofovir levels was 1.08 (95% CI 0.97-1.20). TFV transfer was 60% lower from mothers who had preterm deliveries compared to term and 42% lower from mothers who had C-section deliveries compared to vaginal...

BACKGROUND: Leishmania skin test (LST) evaluates the delayed type hypersensitivity to Leishmania antigens (LA) and has been used for diagnosis of cutaneous leishmaniasis (CL). CL patients usually present a positive LST, but as small percentage have a negative LST (LST-). The aim of this study was to determine the clinic and immunologic features and response to antimony therapy in LST- CL patients. METHODS: Here we compare the clinic presentation, response to therapy and immune response of CL patients with LST- versus LST+...

Nasopharyngeal carcinoma (NPC) is caused by Epstein-Barr virus (EBV) and is more likely to occur in susceptible families. Whether genetic susceptibility operates through altered EBV control is incompletely understood. A NPC risk prediction model based on 14 EBV markers to compare the risk score distribution in unaffected members from multiplex families with that in population-based controls. Despite the absence of NPC at the time of antibody measurement, we still observed an upward shift in the risk score among multiplex family members compared to general population, consistent with the possibility that genetic factors affect NPC risk through alterations in EBV control...

Visceral leishmaniasis (VL; Leishmania donovani) cases produce interferon-γ and tumour necrosis factor in response to soluble leishmanial antigen (SLA) in whole blood assays. Using transcriptional profiling, we demonstrate the impact of interleukin-10 (IL10), a cytokine implicated in VL, on this response. SLA stimulation identified 28 differentially expressed genes (DEGs), 17/28 in a single network with TNF as hub. SLA plus anti-IL10 produced 454 DEGs, 292 in a single network with TNF, IFNG, NFKBIA, IL6 and IL1B as hubs in concert with a remarkable chemokine/cytokine storm...