Verollet, C. | Search bioRxiv

bioRxiv2019

Tuberculosis-associated IFN-I induces Siglec-1 on tunneling nanotubes and favors HIV-1 spread in macrophages

While tuberculosis (TB) is a risk factor in HIV-1-infected individuals, the mechanisms by which Mycobacterium tuberculosis worsens HIV-1 pathogenesis remain poorly understood. Recently, we showed that HIV-1 infection and spread are exacerbated in macrophages exposed to TB-associated microenvironments due to tunneling nanotube (TNT) formation. To identify molecular factors associated with TNT function, we performed a transcriptomic analysis in these macrophages, and revealed the up-regulation of the lectin receptor Siglec-1. We demonstrate Siglec-1 expression depends on TB-mediated production of type I interferon. In co-infected non-human primates, Siglec-1 is highly expressed by alveolar macrophages, whose abundance correlates with pathology and activation of the type I interferon/STAT1 pathway. Intriguingly, Siglec-1 expression localizes exclusively on microtubule-containing TNT that are long and carry HIV-1 cargo. Siglec-1 depletion in macrophages decreases TNT length, diminishes HIV-1 capture and cell-to-cell transfer, and abrogates TB-driven exacerbation of HIV-1 infection. Altogether, we uncover a deleterious role for Siglec-1 in TB-HIV-1 co-infection, and its localization on TNT opens new avenues to understand cell-to-cell viral spread.

cell biology↗

bioRxiv2019

Quantitative proteomics and transcriptomics exploration of primary myeloid cells: importance of β tubulin isotypes for bone resorption.

Among hematopoietic cells. osteoclasts (Oc) and immature dendritic cells (Dc) are closely related myeloid cells with distinct functions; Oc participate skeleton maintenance while Dc sample the environment for foreign antigens. Such specificities rely on profound modifications of gene and protein expression during Oc and Dc differentiation. We provide global proteomic and transcriptomic analyses of primary mouse Oc and Dc. based on original SILAC and RNAseq data. We established specific signatures for Oc and Dc including genes and proteins of unknown functions. In particular. we showed that Oc and Dc have the same and {beta} tubulin isotypes repertoire but that Oc express much more {beta} tubulin isotype Tubb6. In both mouse and human Oc. we demonstrate that elevated expression of Tubb6 in Oc is necessary for correct podosomes organization and thus for the structure of the sealing zone. which sustains the bone resorption apparatus. Hence. lowering Tubb6 expression hindered Oc resorption activity. Overall. we highlight here potential new regulators of Oc and Dc biology and illustrate the functional importance of the tubulin isotype repertoire in the biology of differentiated cells. Summary statementThis study provides original proteomic and transcriptomic data of primary myeloid cells. The analysis led to signatures for osteoclasts and for immature dendritic cells including potential new regulators of their specific biology. RNA interference showed in particular that {beta} tubulin isotype Tubb6 participates in osteoclast podosome patterning. sealing zone structure and in the resorption activity.

cell biology↗