The group Host Targets of Infection (HoTI) investigates the impact of infection on host homeostasis. Using in vitro models, animal experiments and human studies, it contributes to the identification of host targets for treatment, as well as to the development of microbe-directed drugs.
The HoTI group is dedicated to the study of host-pathogen interaction.
We have shown that infections impact the host iron distribution, by pathogen-specific pathways. Mycobacteria cause chronic infections, involving the formation of granulomatous lesions, where iron accumulates. The inflammatory mediators released during infection, notably interferon gamma (IFNG), have a broad impact in host homeostasis. M. avium-infected animals have an IFNG-dependent defective erythropoiesis, leading to the formation of red blood cells with a decreased life span. Increased red blood destruction leads to 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 in the optimization of AMP and other anti-mycobacterial molecules, in collaboration with partners from the Chemistry and Biophysical fields. We are developing better in vitro models to test new compounds.
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: 2] [IF: 5,6]
DOI: 10.3390/ijms23010269 SCOPUS: 85121730455
Gomes A.C., Saraiva M., Gomes M.S.,
The bone marrow hematopoietic niche and its adaptation to infection. Seminars in Cell and Developmental Biology112:37-48, 2021. [Journal: Review] [CI: 9] [IF: 7,5]
DOI: 10.1016/j.semcdb.2020.05.014 SCOPUS: 85086444727
Bento C.M., Gomes M.S., Silva T.,
Looking beyond typical treatments for atypical mycobacteria. Antibiotics9(1):, 2020. [Journal: Review] [CI: 21] [IF: 4,6]
DOI: 10.3390/antibiotics9010018 SCOPUS: 85078224695
Bento C.M., Gomes M.S., Silva T.,
Evolution of antibacterial drug screening methods: Current prospects for mycobacteria. Microorganisms9(12):, 2021. [Journal: Review] [CI: 3] [IF: 4,9]
DOI: 10.3390/microorganisms9122562 SCOPUS: 85120784732
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: 12] [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: 33] [IF: 4,4]
DOI: 10.1038/s41598-020-59898-0 SCOPUS: 85079813225
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
Oliveira T.C., Gomes M.S., Gomes A.C.,
The crossroads between infection and bone loss. Microorganisms8(11):1-18, 2020. [Journal: Review] [CI: 17] [IF: 4,1]
DOI: 10.3390/microorganisms8111765 SCOPUS: 85096078106
Bento C.M., Silva A.T., Mansano B., Aguiar L., Teixeira C., Gomes M.S., Gomes P., Silva T., Ferraz R.,
Improving the Antimycobacterial Drug Clofazimine through Formation of Organic Salts by Combination with Fluoroquinolones. International Journal of Molecular Sciences24(2):, 2023. [Journal: Article] [IF: 5,6 (*)]
DOI: 10.3390/ijms24021402 SCOPUS: 85146797123
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] [IF: 5,5 (*)]
DOI: 10.3390/biom13030425 SCOPUS: 85151109602
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: 20] [IF: 3,6]
DOI: 10.1128/mSphere.00301-17 SCOPUS: 85027999471
Gomes A.C., Moreira A.C., Mesquita G., Gomes M.S.,
Modulation of iron metabolism in response to infection: Twists for all tastes. Pharmaceuticals11(3):, 2018. [Journal: Review] [CI: 25]
DOI: 10.3390/ph11030084 SCOPUS: 85053844480