Innate myeloid cell TNFR1 mediates first line defence against primary Mycobacterium tuberculosis infection.

TNF is crucial for controlling Mycobacterium tuberculosis infection and understanding how will help immunomodulating the host response. Here we assessed the contribution of TNFR1 pathway from innate myeloid versus T cells. We first established the prominent role of TNFR1 in haematopoietic cells for controlling M. tuberculosis in TNFR1 KO chimera mice. Further, absence of TNFR1 specifically on myeloid cells (M-TNFR1 KO) recapitulated the uncontrolled M. tuberculosis infection seen in fully TNFR1 deficient mice, with increased bacterial burden, exacerbated lung inflammation, and rapid death. Pulmonary IL-12p40 over-expression was attributed to a prominent CD11b(+) Gr1(high) cell population in infected M-TNFR1 KO mice. By contrast, absence of TNFR1 on T-cells did not compromise the control of M. tuberculosis infection over 6-months. Thus, the protective TNF/TNFR1 pathway essential for controlling primary M. tuberculosis infection depends on innate macrophage and neutrophil myeloid cells, while TNFR1 pathway in T cells is dispensable.

[Extracranial stereotaxic body irradiation: preliminary results and the Orleans hospital experience]. / La radiothérapie stéréotaxique extracrânienne: résultats préliminaires et expérience de l'hôpital d'Orléans.

Extracranial stereotactic body irradiation (ESRT) provides an alternative treatment mode for patients with no other therapeutic solutions. It's based on previous intracranial stereotactic radiosurgery techniques. ESRT with dedicated systems including secure immobilization avoiding patient movement, accurate repositioning, and stereotactic registration of tumor targets and organs at risk (OAR) allows very high doses in few fractions on extra cranial locations. Standard linacs permit performing SBRT with specific immobilization devices including stereotactic location of the target. Different schemes of ESRT have been published. Comparison of these very diverse schemes is not easy since the prescription mode on target volumes and OAR are not always clearly defined. The Radiotherapy Department of Orléans Hospital chose to set up the ESRT on a conventional accelerator using an immobilization device including a Stereotactic Body Frame and an Active Breathing Control system (Elekta). From 120 patients treated with ESRT since 1999, 90 cases are presented; 28 lung metastases were treated with 40 Gy/5 fr/12 d and 17 liver metastases were treated with 30 Gy/5 fr/12 d prescribed on the 70 to 85 % isodose. The local control was obtained in 50 % of the cases. Twenty-eight patients were treated for T1-T2 N0 lung cancer with 50 Gy/10 fr/12 d on the 80 % isodose. Local control was obtained in 50 % of the cases. Seventeen liver cancers were treated with 30 Gy/10 fr/15 d prescribed on the 70 to 80 % isodose. Local control was obtained in 47 % of the cases. ECRT allows controlling localized tumors (primitives or metastases) and it is now a suitable part of our therapeutic tools as radiofrequency or cryotherapy techniques. Phase II studies are required to confirm its therapeutic potential.