During infection, successful pathogens establish themselves into the host by evading immune responses. We investigate the mechanistic interplay between innate immune cells and pathogens.
More specifically, we study the following questions:
1. How does mycobacteria survive in macrophages?
2. How does flavivirus exploit IFN signaling?
3. How do neutrophils regulate tissue damage in sepsis?
4. What microbial associated molecular determinants regulate infection and bystander cell responses?
Flavivirus research: The evolutionary arms race between viruses and its hosts led to evolution of immune evasion mechanisms that are crucial for successful viral replication. Considering IFN-I’s importance in viral infection control, many immunomodulatory proteins target this signaling pathway. The compact flavivirus genome encodes seven non-structural proteins that are responsible for viral replication and immune evasion. Our goal is to unveil the interplay between the host immune system and viral evasion mechanisms. Understanding these mechanisms will allow the definition of targets for drugs and vaccine development.
Mycobacteria research: Pathways involved in pathogen recognition by myeloid cells orchestrate the immune system to eliminate infection. Receptors expressed on myeloid cells as well as pathogen-derived factors are thought to be critical to the outcome of optimal host immunity. Several pattern recognition receptors have been demonstrated to sense Mycobacterium tuberculosis (Mtb), a human specific pathogen. In contrast, mycobacteria-secreted components impact immune responses and influence protection in vivo. Our long-term goal is to elucidate the mechanisms by which Mtb regulates immune responses in humans. Uncovering these mechanisms will lead to novel avenues to design better vaccines and host-directed therapies to major human diseases.
Neutrophil Biology research: Neutrophil migration to the focus of infection is key for bacterial clearance. However, overstimulation of circulating neutrophils leads to their infiltration in vital organs with consequent damage to the host. We study the molecular mechanisms involved in neutrophil response to find new ways to prevent cell overstimulation without changing their microbicidal response.
Fajardo T et al. The flavivirus polymerase NS5 regulates translation of viral genomic RNA. Nucleic Acids Res. 2020;48(9):5081-5093.
Delgobo M et al. An evolutionary recent IFN/IL-6/CEBP axis is linked to monocyte expansion and tuberculosis severity in humans. Elife. 2019 Oct 22;8.
Dos Santos PF et al. ISG15-Induced IL-10 Is a Novel Anti-Inflammatory Myeloid Axis Disrupted during Active Tuberculosis. J Immunol. 2018 Feb 15;200(4):1434-1442.
Spiller F et al. Murine Red Blood Cells Lack Ligands for B Cell Siglecs, Allowing Strong Activation by Erythrocyte Surface Antigens. J Immunol. 2018;200(3):949-956.
Soares FS et al. Antibiotic-Induced Pathobiont Dissemination Accelerates Mortality in Severe Experimental Pancreatitis. Front Immunol. 2017;8:1890.
Yamashiro LH et al. Isoniazid-induced control of Mycobacterium tuberculosis by primary human cells requires interleukin-1 receptor and tumor necrosis factor. Eur J Immunol. 2016 Aug;46(8):1936-47.
Ferguson BJ, Mansur DS, Peters NE, Ren H, Smith GL. DNA-PK is a DNA sensor for IRF-3-dependent innate immunity. Elife. 2012;1:e00047.
Bafica A, Scanga CA, Feng CG, Leifer C, Cheever A, Sher A. TLR9 regulates Th1 responses and cooperates with TLR2 in mediating optimal resistance to Mycobacterium tuberculosis. J Exp Med. 2005;202(12):1715-1724.
Bafica A, Scanga CA, Serhan C, et al. Host control of Mycobacterium tuberculosis is regulated by 5-lipoxygenase-dependent lipoxin production. J Clin Invest. 2005;115(6):1601-1606.