Tuberculosis/HIV-1 co-infection is responsible for thousands of deaths each year, and previous studies have reported that co-infected individuals display major morphological alterations in tissue granulomas. The purpose of this study was to evaluate immunohistopathological characteristics in lung tissues from pulmonary TB/HIV-1-co-infected individuals. Following autopsy, tuberculosis-positive HIV-1-negative cases displayed granulomas with normal architecture, mainly composed of a mononuclear infiltrate with typical epithelioid, as well as giant cells, and exhibiting caseous necrosis. In contrast, lesions from the TB/HIV-1-co-infected group showed extensive necrosis, poorly formed granulomas, and a marked presence of polymorphonuclear cells. More importantly, TNF staining was greatly reduced in the TB/HIV-1-co-infected individuals. Our data suggest that HIV-1 infection alters the organization of pulmonary granulomas by modulating TNF and, possibly, cell trafficking, leading to an impaired anti-tuberculosis response.

Type I interferons (IFNs) are cytokines that orchestrate diverse immune responses to viral and bacterial infections. Although typically considered to be most important molecules in response to viruses, type I IFNs are also induced by most, if not all, bacterial pathogens. In this study, we addressed the role of type I IFN signaling during Brucella abortus infection, a facultative intracellular bacterial pathogen that causes abortion in domestic animals and undulant fever in humans. Herein, we have shown that B. abortus induced IFN-β in macrophages and splenocytes. Further, IFN-β induction by Brucella was mediated by IRF3 signaling pathway and activates IFN-stimulated genes via STAT1 phosphorylation. In addition, IFN-β expression induced by Brucella is independent of TLRs and TRIF signaling but MyD88-dependent, a pathway not yet described for Gram-negative bacteria. Furthermore, we have identified Brucella DNA as the major bacterial component to induce IFN-β and our study revealed that this molecule operates through a mechanism dependent on RNA polymerase III to be sensed probably by an unknown receptor via the adaptor molecule STING. Finally, we have demonstrated that IFN-αβR KO mice are more resistant to infection suggesting that type I IFN signaling is detrimental to host control of Brucella. This resistance phenotype is accompanied by increased IFN-γ and NO production by IFN-αβR KO spleen cells and reduced apoptosis.

Taken together, our results reveal the existence of an intracellular selection process in macrophages that favors TcII, but not TcI, when infection occurs with vector-derived mixed TcI/TcII strains.

In this study, we have identified a secreted 13 kDa lectin from Mtb (Mtb, Mycobacterium tuberculosis; sMTL-13) by homology search of a non-redundant lectin database. Bioinformatic analysis revealed that sMTL-13 belongs to the ricin-type b-trefoil family of proteins containing a Sec-type signal peptide present in Mtb complex species, but not in nontuberculous mycobacteria. Following heterologous expression of sMTL-13 and generation of an mAb (clone 276.B7/IgG1j), we confirmed that this lectin is present in culture filtrate proteins from Mtb H37Rv, but not in non-tuberculous mycobacteria-derived culture filtrate proteins. In addition, sMTL-13 leads to an increased IFN-c production by PBMC from active tuberculosis (ATB) patients. Furthermore, sera from ATB patients displayed high titers of IgG Ab against sMTL-13, a response found to be decreased following successful antituberculosis therapy. Together, our findings reveal a secreted 13 kDa ricin-like lectin from Mtb, which is immunologically recognized during ATB and could serve as a biomarker of disease treatment.