Where Ideas Grow

Host Targets of Infection


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.

Liver section from a mouse infected with Mycobacterium avium. Different cell types can be seen, as well as collagen fibres, typical of granulomatous lesions.


Selected Publications

Gomes A.C., Sousa D.M., Oliveira T.C., Fonseca Ó., Pinto R.J., Silvério D., Fernandes A.I., Moreira A.C., Silva T., Teles M.J., Pereira L., Saraiva M., Lamghari M., Gomes M.S.,
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

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

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

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., 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] [CI: 1] [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] [CI: 2] [IF: 5,5 (*)]
DOI: 10.3390/biom13030425 SCOPUS: 85151109602

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

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

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: 27]
DOI: 10.3390/ph11030084 SCOPUS: 85053844480

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

Ongoing Projects

Otimizar Péptidos Antimicrobianos usando estratégias de ponta para combater infeções causadas por micobactérias não-tuberculosas
Reference: PTDC/BIA-MIC/3458/2020
Proponent: Instituto de Investigação e Inovação em Saúde - Universidade do Porto
Sponsor: FCT - Fundação para a Ciência e a Tecnologia
From 01-APR-21 to 31-DEC-24
Identification of mechanisms and biomarkers of bone loss in patients with Cystic Fibrosis
Reference: CFF Research Grants - Fall 2021 - BoneSAAver
Proponent: Instituto de Investigação e Inovação em Saúde - Universidade do Porto
Sponsor: Cystic Fibrosis Foundation
From 01-MAY-22 to 30-APR-24
The macrophage – hepatocyte iron communication during mycobacterial infection
Reference: 2022.03635.PTDC
Proponent: Instituto de Investigação e Inovação em Saúde - Universidade do Porto
Sponsor: FCT - Fundação para a Ciência e a Tecnologia
From 01-MAR-23 to 31-AUG-24