T cell receptor (TCR) Vγ4-expressing γδ T cells comprise interferon γ (IFNγ)- and interleukin-17 (IL-17)-producing effector subsets, with a preference for IL-17 effector fate decisions during early ...ontogeny. The existence of adult-thymus-derived IL-17+ T cells (γδ17) remains controversial. Here, we use a mouse model in which T cells are generated exclusively in the adult thymus and employ single-cell chromatin state analysis to study their development. We identify adult-thymus-derived Vγ4 T cells that have all the molecular programs to become IL-17 producers. However, they have reduced IL-17 production capabilities and rarely reach the periphery. Moreover, this study provides high-resolution profiles of Vγ4 T cells in the adult thymus and lymph nodes and identifies Zeb1 as a potential γδ17 cell regulator. Together, this study provides valuable insights into the developmental traits of Vγ4 T cells during adulthood and supports the idea of age-specific signals required for thymic export and/or peripheral maturation of γδ17 cells.
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•Molecular profiling identifies developmental plasticity of Vγ4 T cells in adult thymus•A hypomorphic mutation of Zeb1 perturbs γδ17 cells•c-Maf+ RORγt+ Vγ4 T cells that can produce IL-17 are generated from adult thymic precursors•De novo-generated Vγ4+ γδ17 cells of the adult thymus do not reach the periphery
The existence of postnatal-derived IL-17-producing γδ T cells remains controversial. Yang et al. identify de novo-generated Vγ4 T cells harboring molecular programs of IL-17 producers in adult thymus. However, these c-Maf+ RORγt+ Vγ4 T cells did not reach the periphery nor did they mature into CD44high effector cells.
Preterm infants are at high risk of developing neonatal sepsis. γδ T cells are thought to be an important set of effector cells in neonates. Here, γδ T cells were investigated in a longitudinal ...cohort of preterm neonates using next-generation sequencing, flow cytometry, and functional assays. During the first year of life, the Vγ9Vδ2 T cell subset showed dynamic phenotypic changes and elevated levels of fetal-derived Vγ9Vδ2 T cells were evident in infants with sepsis. Single-cell transcriptomics identified HLA-DRhiCD83+ γδ T cells in neonatal sepsis, which expressed genes related to antigen presentation. In vitro assays showed that CD83 was expressed on activated Vγ9Vδ2 T cells in preterm and term neonates, but not in adults. In contrast, activation of adult Vγ9Vδ2 T cells enhanced CD86 expression, which was presumably the key receptor to induce CD4 T cell proliferation. Together, we provide a map of the maturation of γδ T cells after preterm birth and highlight their phenotypic diversity in infections.
Mendelian susceptibility to mycobacterial disease (MSMD) is a rare genetic disorder characterized by impaired immunity against intracellular pathogens, such as mycobacteria, attenuated
Mycobacterium ...bovis
-Bacillus Calmette–Guérin (BCG) vaccine strains, and environmental mycobacteria in otherwise healthy individuals. Retrospective study reviewed the clinical, immunological, and genetic characteristics of patients with MSMD in Mexico. Overall, 22 patients diagnosed with MSMD from 2006 to 2021 were enrolled: 14 males (64%) and eight females. After BCG vaccination, 12 patients (70%) developed BCG infection. Furthermore, 6 (22%) patients developed bacterial infections mainly caused by
Salmonella
, as what is described next in the text is fungal infections, particularly Histoplasma. Seven patients died of disseminated BCG disease. Thirteen different pathogenic variants were identified in
IL12RB1
(
n
= 13),
IFNGR1
(
n
= 3), and
IFNGR2
(
n
= 1) genes. Interleukin-12Rβ1 deficiency is the leading cause of MSMD in our cohort. Morbidity and mortality were primarily due to BCG infection.
Background and aims
Many improvements have been made in the treatment of human immunodeficiency virus (HIV) in pediatric patients; however, challenges remain in terms of achieving normal growth, body ...composition, and metabolism during treatment, etc. Current nutritional recommendations are based on studies performed in adults, with limited data on the HIV-infected pediatric population. Therefore, this study aimed to compare the resting energy expenditure (REE) of asymptomatic HIV-infected pediatric patients with healthy counterparts and to compare body composition, dietary intake, and physical activity between the two groups.
Methods
This was a cross-sectional study of asymptomatic HIV-infected children who were receiving antiretroviral therapy; the infected group was compared with the uninfected group, matched by age (± 6 months), sex, and body mass index (± 0.5 z-score). Participants were recruited between 2021 and 2022, as outpatients. In both groups, REE was determined by indirect calorimetry and body composition by bioelectrical impedance analysis and hand strength, measured using a hydraulic hand dynamometer.
Results
Seventy-eight participants were enrolled, where
n
= 39 HIV-infected children and
n
= 39 controls, with a mean age of 11.6 ± 3.4 years old. REE was significantly higher in the HIV group (1254.4 ± 334.7 kcal/day vs. 1124.7 ± 321 kcal/day,
p
= 0.013) than in the control group. Fat-free mass (FFM) was lower in the HIV group (28.2 ± 10.5 kg vs. 32 ± 11.2 kg,
p
= 0.001); this trend continued when the index skeletal muscle was evaluated (7.2 ± 1.2 vs. 7.6 ± 1.5,
p
= 0.04). The strength of the dominant hand was also lower in the HIV group (12 (8–18) kg vs. 20 (10.5–26) kg,
p
< 0.0001).
Conclusions
Children with asymptomatic HIV infection have higher REE than their uninfected peers. They also present decreased FFM, skeletal muscle mass index, and muscle strength. These parameters should be considered during nutritional assessment in this population to have a favorable impact on nutritional status and growth.
Introducción: La enfermedad granulomatosa crónica (EGC) es un error innato de la inmunidad, se caracteriza por una susceptibilidad a padecer infecciones bacterianas y fúngicas y a una falta de ...regulación inflamatoria sistémica. Las variantes patogénicas en el gen CYBB se trasmiten con un patrón de herencia ligada al X; mientras que las variantes patogénicas presentes en los genes EROS, NCF1, NCF2, NCF4 o CYBA se trasmiten con un patrón de herencia autosómico recesivo.
Objetivos. Describir las características clínicas, inmunológicas y genéticas de dos pacientes con EGC e infección por BCG.
Métodos: En neutrófilos de sangre periférica se midió la producción de H2O2 y la expresión de las subunidades de la NADPH oxidasa. La detección de las variantes patogénicas fue por secuenciación Sanger del gen NCF2. La información clínica fue extraída de los expedientes por los médicos tratantes.
Resultados: Presentamos a dos lactantes masculinos de dos familias no relacionadas de la etnia maya, con EGC e infección por la vacuna de BCG. Se identificaron tres diferentes variantes patogénicas en el gen NCF2; por un lado, c.304 C>T (p.Arg102*) ya reportada, por otro lado, c.1369 A>T (p.Lys457*) y c.979 G>T (p.Gly327*) no reportadas.
Conclusiones: En pacientes con infección micobacteriana por BCG debemos sospechar en un error innato de la inmunidad, como la EGC. El diagnóstico de EGC se realiza a través de la detección de una falta de producción de radicales libres en los neutrófilos. Los pacientes reportados tuvieron variantes patogénicas en el gen NCF2, dos de ellas no han sido reportadas previamente en la literatura.
Stethoscopes can take part in the transmission of health care-associated infections. We cultured 112 stethoscopes by direct imprint on blood agar to estimate the prevalence of potentially pathogenic ...microorganisms. Forty-eight (47%) produced 50 potentially pathogenic microorganisms; from these, 43 (86%) were Staphylococcus aureus , of which 18 (42%) were methicillin-resistant S. aureus . We concluded that stethoscopes should be considered as potential fomites and must be disinfected routinely before and after each patient contact.
Chromoblastomycosis is a chronic subcutaneous mycosis caused by traumatic inoculation of dematiaceous fungi especially in tropical and subtropical areas. Cyphellophora genus include melanized fungi ...reported as etiological agents of skin and nail infections. We report a 60-year-old male from the south of Mexico with a 40-year history of chromoblastomycosis caused by Cyphellophora laciniata. The isolated fungus was identified by sequencing of the internal transcribed spacer region of rDNA. The patient was treated with itraconazole and cryosurgery with unsatisfactory results.
Effector capabilities of γδ T cells are evident in
infection in young and adult individuals, while children are the most vulnerable groups affected by malaria. Here, we aimed to investigate the ...age-dependent phenotypic composition of Vδ1
, Vδ2
, and Vδ3
T cells in children living in endemic malaria areas and how this differs between children that will develop symptomatic and asymptomatic
infections. Flow cytometric profiling of naïve and effector peripheral blood γδ T cells was performed in 6 neonates, 10 adults, and 52 children. The study population of young children, living in the same malaria endemic region of Ghana, was monitored for symptomatic
asymptomatic malaria development for up to 42 weeks after peripheral blood sampling at baseline. For the Vδ2
T cell population, there was evidence for an established type 1 effector phenotype, characterized by CD94 and CD16 expression, as early as 1 year of life. This was similar among children diagnosed with symptomatic or asymptomatic malaria. In contrast, the proportion of type 2- and type 3-like Vδ2 T cells declined during early childhood. Furthermore, for Vδ1
and Vδ3
T cells, similar phenotypes of naïve (CD27
) and type 1 effector (CD16
) cells were observed, while the proportion of CD16
Vδ1
T cells was highest in children with asymptomatic malaria. In summary, we give evidence for an established adult-like γδ T cell compartment in early childhood with similar biology of Vδ1
and Vδ3
T cells. Moreover, the data supports the idea that type 1 effector Vδ1
T cells mediate the acquisition of and can potentially serve as biomarker for natural immunity to
infections in young individuals from malaria-endemic settings.
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