Host Targets of Infection
ABOUT
The group Host Targets of Infection (HoTI) investigates the impact of chronic infection on host homeostasis, with a special interest on Non-Tuberculous Mycobacteria (NTM). Using in vitro models, animal experiments and human studies, it contributes to the elucidation of mechanisms of disease, as well as to the development of both host-targeted and microbe-targeted drugs.
RESEARCH
Regarding the impact of chronic infection on host homeostasis, we are especially interested in iron-related alterations. We found that infections by mycobacteria cause a notorious iron re-distribution in the host. The inflammatory mediators released during infection, namely interferon gamma (IFNG), cause defective erythropoiesis, leading to the formation of red blood cells with a decreased life span. Increased red blood cell destruction leads to intra-macrophagic iron accumulation and oxidative stress, contributing to pathology. In this context, the iron-binding capacity of H-ferritin exerts an important protective effect.
Iron withholding plays a key role in the host’s protection against infection, but other mechanisms are also important. Macrophages and neutrophils produce several molecules with significant antimicrobial activity, namely antimicrobial peptides (AMP). AMP derived from lactoferrin can inhibit the growth of mycobacteria, both through direct mechanisms and through the modulation of the antimicrobial activity of macrophages. The HoTI group is working on the optimization of AMP and other anti-mycobacterial molecules, for future therapeutic use. For this, we have optimized drug screening assays, based on fluorescent and luminescent strains of M. avium and M. abscessus, encompassing simple direct activity on planktonic bacteria, but also biofilm and macrophage infection models.
Team
Selected Publications
Serum amyloid A proteins reduce bone mass during mycobacterial infections. Frontiers in Immunology14:, 2023. [Journal: Article] [IF: 7,3 (*)]
DOI: 10.3389/fimmu.2023.1168607 SCOPUS: 85158023043
Fonseca Ó., Gomes M.S., Amorim M.A., Gomes A.C.,
Cystic Fibrosis Bone Disease: The Interplay between CFTR Dysfunction and Chronic Inflammation. Biomolecules13(3):, 2023. [Journal: Review] [CI: 2] [IF: 5,5 (*)]
DOI: 10.3390/biom13030425 SCOPUS: 85151109602
Moreira A.C., Silva T., Mesquita G., Gomes A.C., Bento C.M., Neves J.V., Rodrigues D.F., Rodrigues P.N., Almeida A.A., Santambrogio P., Gomes M.S.,
H-ferritin produced by myeloid cells is released to the circulation and plays a major role in liver iron distribution during infection. International Journal of Molecular Sciences23(1):, 2022. [Journal: Article] [CI: 7] [IF: 5,6]
DOI: 10.3390/ijms23010269 SCOPUS: 85121730455
Moreira A.C., Teles M.J., Silva T., Bento C.M., Alves I.S., Pereira L., Guimarães J.T., Porto G., Oliveira P., Gomes M.S.,
Iron related biomarkers predict disease severity in a cohort of portuguese adult patients during covid-19 acute infection. Viruses13(12):, 2021. [Journal: Article] [CI: 13] [IF: 5,8]
DOI: 10.3390/v13122482 SCOPUS: 85121430002
Mesquita G., Silva T., Gomes A.C., Oliveira P.F., Alves M.G., Fernandes R., Almeida A.A., Moreira A.C., Gomes M.S.,
H-Ferritin is essential for macrophages’ capacity to store or detoxify exogenously added iron. Scientific Reports10(1):, 2020. [Journal: Article] [CI: 39] [IF: 4,4]
DOI: 10.1038/s41598-020-59898-0 SCOPUS: 85079813225
Moreira A.C., Mesquita G., Gomes M.S.,
Ferritin: An inflammatory player keeping iron at the core of pathogen-host interactions. Microorganisms8(4):, 2020. [Journal: Review] [CI: 63] [IF: 4,1]
DOI: 10.3390/microorganisms8040589 SCOPUS: 85083773336
Gomes A.C., Moreira A.C., Silva T., Neves J.V., Mesquita G., Almeida A.A., Barreira-Silva P., Fernandes R., Resende M., Appelberg R., Rodrigues P.N.S., Gomes M.S.,
IFN-γ-dependent reduction of erythrocyte life span leads to anemia during mycobacterial infection. Journal of Immunology203(9):2485-2496, 2019. [Journal: Article] [CI: 22] [IF: 4,9]
DOI: 10.4049/jimmunol.1900382 SCOPUS: 85073667610
Bento C.M., Gomes M.S., Silva T.,
Evolution of antibacterial drug screening methods: Current prospects for mycobacteria. Microorganisms9(12):, 2021. [Journal: Review] [CI: 4] [IF: 4,9]
DOI: 10.3390/microorganisms9122562 SCOPUS: 85120784732
Bento C.M., Gomes M.S., Silva T.,
Looking beyond typical treatments for atypical mycobacteria. Antibiotics9(1):, 2020. [Journal: Review] [CI: 29] [IF: 4,6]
DOI: 10.3390/antibiotics9010018 SCOPUS: 85078224695
Silva T., Moreira A.C., Nazmi K., Moniz T., Vale N., Rangel M., Gomes P., Jan J.G., Rodrigues P.N., Bastos M., Gomes M.S.,
Lactoferricin peptides increase macrophages' capacity to kill Mycobacterium avium. mSphere2(4):, 2017. [Journal: Article] [CI: 21] [IF: 3,6]
DOI: 10.1128/mSphere.00301-17 SCOPUS: 85027999471