Comparative genomic and phylogeographic analysis of Mycobacterium leprae.

Reductive evolution and massive pseudogene formation have shaped the 3.31-Mb genome of Mycobacterium leprae, an unculturable obligate pathogen that causes leprosy in humans. The complete genome sequence of M. leprae strain Br4923 from Brazil was obtained by conventional methods (6x coverage), and Illumina resequencing technology was used to obtain the sequences of strains Thai53 (38x coverage) and NHDP63 (46x coverage) from Thailand and the United States, respectively. Whole-genome comparisons with the previously sequenced TN strain from India revealed that the four strains share 99.995% sequence identity and differ only in 215 polymorphic sites, mainly SNPs, and by 5 pseudogenes. Sixteen interrelated SNP subtypes were defined by genotyping both extant and extinct strains of M. leprae from around the world. The 16 SNP subtypes showed a strong geographical association that reflects the migration patterns of early humans and trade routes, with the Silk Road linking Europe to China having contributed to the spread of leprosy.

Dominant TNF-α(+) Mycobacterium tuberculosis-specific CD4(+) T cell responses discriminate between latent infection and active disease.

Rapid diagnosis of active Mycobacterium tuberculosis (Mtb) infection remains a clinical and laboratory challenge. We have analyzed the cytokine profile (interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α) and interleukin-2 (IL-2)) of Mtb-specific T cells by polychromatic flow cytometry. We studied Mtb-specific CD4(+) T cell responses in subjects with latent Mtb infection and active tuberculosis disease. The results showed substantial increase in the proportion of single-positive TNF-α Mtb-specific CD4(+) T cells in subjects with active disease, and this parameter was the strongest predictor of diagnosis of active disease versus latent infection. We validated the use of this parameter in a cohort of 101 subjects with tuberculosis diagnosis unknown to the investigator. The sensitivity and specificity of the flow cytometry-based assay were 67% and 92%, respectively, the positive predictive value was 80% and the negative predictive value was 92.4%. Therefore, the proportion of single-positive TNF-α Mtb-specific CD4(+) T cells is a new tool for the rapid diagnosis of active tuberculosis disease.

Leucograma en novillas y becerros (Holstein) infectados con una cepa venezolana de Trypanosoma vivax

Este trabajo tuvo como objetivo la evaluación del leucograma en novillas y becerros Holstein infectados experimentalmente con una cepa venezolana de Trypanosoma vivax. Los datos fueron analizados a través de la prueba no paramétrica de U de Mann-Whitney. La comparación de las medias de los numeros totales de los leucocitos (NTL) en las novillas, fue estadísticamente significativo (P < 0,05). Los becerros presentaron neutrofilia al compararse las medias totales del grupo infectado y control (P < 0,05). Los promedios totales de los linfocitos y monocitos en las novillas y becerros, fueron estadísticamente significativos (P < 0,05).

Mycobacterium tuberculosis-specific CD8 T cells are functionally and phenotypically different between latent infection and active disease

Purpose/Objective: Tuberculosis (TB) is the second worldwide leading cause of death from an infectious disease after HIV infection. Protective immunity to Mycobacterium tuberculosis (Mtb) remains poorly understood and the role of Mtb-specific CD8 T-cells is controversial. We performed comprehensive functional and phenotypic characterizations of Mtb-specific CD8 T-cell responses in 273 subjects with either latent Mtb infection (LTBI) or active TB disease (TB) to assess their profile and relevance in TB. Materials and methods: Using multi-parametric flow cytometry, we assessed Mtb-specific CD8 T-cell functional (production of IFNgamma, IL-2 and TNF-alpha; proliferation capacity and cytotoxicity) and phenotypic (T-cell differentiation and exhaustion) profiles in cells isolated from peripheral blood and correlated these profiles with distinct clinical presentations. Results: Mtb-specific CD8 T-cells were detected in most TB patients and few LTBI subjects (65% and 15%, respectively; P < 0.00001) and were of similar magnitude with a comparable cytokines profile (IFNg+TNFa+IL2-) in both groups. Mtb-specific CD8 T-cells were mostly TEMRA (CD45RA+ CCR7-) co-expressing 2B4 and CD160 in LTBI subjects and mostly TEM (CD45RA-CCR7-) lacking PD-1/ CD160/2B4 in TB patients. Furthermore, Mtb-specific CD8 T-cells mostly expressed very little perforin and granulysin but contained granzymes A and B or lacked all these cytotoxic markers in TB and LTBI subjects, respectively. However, in vitro expanded Mtb-specific CD8 T-cells acquired perforin, granulysin and granzymes. Finally, Mtb-specific CD8 T-cell responses were more robust and prone to proliferate in patients with extrapulmonary compared to pulmonary TB. Conclusions: The clinical status and TB presentation are associated to specific profiles of Mtb-specific CD8 T-cell responses, thus indicating distinct dynamics between the mycobacteria, the CD8 T-cell response and the clinical outcome. Our data shed light on the controversial reached by studies performed in human and animal models, thus advancing the current knowledge on the complex dynamic of TB immunity.

1.° Pompeii commentarius in artem Donati. — 2.° Ars Capri de orthographia ; sive Flavii Capri, Grammatici vetustissimi, libellus de orthographia. — 3.° Agroecii libellus de orthographia, proprietate et differentia sermonis, ad Eucherium Episcopum ; editus in supplementum libri Flavii Capri de eodem argumento : sub finem multa desiderantur. — 4.° Anonymus de verbo, casibus et analogia. — 5.° Anonymi versus de veritate, de fide catholica, de spe, de misericordia et charitate. — 6.° Anonymus de metrorum generibus. — 7.° Sergii commentarius de litteris. — 8.° Maximi Victorini commentarius de ratione metrorum. — 9.° Metrorius de metris : in editis Maximo Victorino, in codice autem Basileensi Servio Honorato tribuitur. — 10.° Marii Servii Honorati, Grammatici, centimetrum.

Faurianus

Mycobacterium avium subsp. paratuberculosis in an Italian Cohort of Type 1 Diabetes Pediatric Patients.

Mycobacterium avium subsp. paratuberculosis (MAP) is the etiological agent of Johne's disease in ruminants. Recent studies have linked MAP to type 1 diabetes (T1D) in the Sardinian population. The aim of this study was to investigate the prevalence of MAP infection in a T1D cohort from continental Italy compared with healthy control subjects. 247 T1D subjects and 110 healthy controls were tested for the presence of MAP. MAP DNA was detected using IS900-specific polymerase chain reaction (PCR). The presence of antibodies towards a MAP antigen, heparin binding hemoagglutinin (HBHA), was detected by ELISA. We demonstrated a higher MAP DNA prevalence in plasma samples from T1D patients and a stronger immune response towards MAP HBHA, compared with healthy control subjects. Moreover, in the recent onset patients, we observed an association between anti-MAP antibodies and HLA DQ2 (DQA1 0201/DQB1 0202). These findings taken together support the hypothesis of MAP as an environmental risk factor for the development of T1D in genetically predisposed subjects, probably involving a mechanism of molecular mimicry between MAP antigens and pancreatic islet β-cells.

1.° Anonymi tractatus de compositione astrolabii. — 2.° Theorica planetarum : authore Gerardo Carmonensi. — 3.° Joannis de Sacrobosco tractatus de sphaera : multa sub finem desiderantur. — 4.° Practica ad componendum cylindrum. — 5.° Compositio astrolabii nova. — 6.° Canones quadrantis novi. — 7.° Canones cylindri. — 8.° Canones astrolabii. — 9.° Anonymi tractatus de compositione sphaerae solidae cum armillis. — 10.° Anonymi practica de modo mensurandi in geometria. — 11.° Algorismus specialis et astronomicus. — 12.° La maniére de connoistre les heures de nuit. — 13.° Anonymi tractatus de compositione quadrantis. — 14.° Canones, sive utilitates quadrantis.

Colbertinus