Host-pathogen interaction
Tipologia: Malattie Infettive
Principal Investigator: Dott. Borghesi Alessandro
Our research group is devoted to the study of inborn errors of immunity (IEI), with a particular interest in those predisposing to viral, bacterial and fungal infections. We aim to understand why some individuals are uniquely susceptible to life-threatening infectious diseases. Using state-of-the-art genomic technologies and immunological testing, including exome and genome sequencing, genome-wide association studies, and screening for cytokine-neutralizing auto-antibodies, we investigate the molecular and cellular mechanisms underlying the interindividual variability of clinical outcome following exposure to a microorganism. We explore how genes and the immune system operate at the individual and population levels, and how this translates into individual resistance or vulnerability to a given microorganism. With a primary focus on the maternal-fetal unit and early post-natal life, we study infections occurring at any age, including those typically affecting the elderly. Our ultimate goal is to identify individuals at risk of severe infection or immune disorders, and to prevent currently unpredictable, potentially fatal conditions.
- Gervais A, Trespidi F, Ferrari A, Rovida F, Marchal A, Croce S, Cassaniti I, Moratti M, Uhrlaub JL, Florian DM, Stiasny K, Burdino E, Angelini M, Bizien L, Lilleri D, Codullo V, Freund T, Paran Y, Gadoth A, Biran R, Mancon A, Lucca C, Vogiatzis S, Pacenti M, Aubart M, Zecca M, Comoli P, Avanzini MA, Fellay J, Piralla A, Conti F, Dolci A, Barzon L, Ghisetti V, Lazzarotto T, Cereda D, Aiuti A, Jouanguy E, Bastard P, MacDonald MR, Rice CM, Puel A, Abel L, Rossini G, Mileto D, Simonin Y, Nagy A, Hagin D, Murray KO, Baldanti F, Aberle JH, Cobat A*, Zhang SY*, Casanova JL*, Borghesi A*. Autoantibodies neutralizing type I IFNs in 40% of patients with WNV encephalitis in seven new cohorts. J Hum Immun. 2026 Mar 13;2(3):e20250189. doi: 10.70962/jhi.20250189. PMID: 41836040
- Rhyn MI, Castellano A, Cortesi V, Trojman NE, Borghesi A. Predisposition to viral infection of the fetus and neonate. Curr Opin Virol. 2026 Apr;75:101520. doi: 10.1016/j.coviro.2026.101520. PMID: 41795233 (Review)
- Ferrari A°, Cassaniti I°, Rovida F, Lilleri D, Croce S, Trespidi F, Ghirardello S, Gervais A, Zhang SY, Casanova JL, Borghesi A*, Baldanti F*. Human type I interferons protect Vero E6 and ARPE-19 cells against West Nile virus and are neutralized by pathogenic autoantibodies. Sci Rep. 2025 Apr 2;15(1):11271. doi: 10.1038/s41598-025-89312-6. PMID: 40175402
- Gervais A*, Borghesi A*, Casanova JL*, Zhang SY*. Auto-Abs against type I IFNs: Strong, common, and global determinants of severe arboviral diseases. J Hum Immun. 2025 Oct 23;2(1):e20250090. doi: 10.70962/jhi.20250090. PMID: 41608126 (Review)
- Gervais A°, Rovida F°, Avanzini MA°, Croce S°, Marchal A, Lin SC, Ferrari A, Thorball CW, Constant O, Le Voyer T, Philippot Q, Rosain J, Angelini M, Pérez Lorenzo M, Bizien L, Achille C, Trespidi F, Burdino E, Cassaniti I, Lilleri D, Fornara C, Sammartino JC, Cereda D, Marrocu C, Piralla A, Valsecchi C, Ricagno S, Cogo P, Neth O, Marín-Cruz I, Pacenti M, Sinigaglia A, Trevisan M, Volpe A, Marzollo A, Conti F, Lazzarotto T, Pession A, Viale P, Fellay J, Ghirardello S, Aubart M, Ghisetti V, Aiuti A, Jouanguy E, Bastard P, Percivalle E, Baldanti F, Puel A, MacDonald MR, Rice CM, Rossini G, Murray KO, Simonin Y, Nagy A, Barzon L, Abel L, Diamond MS, Cobat A*, Zhang SY*, Casanova JL*, Borghesi A*. Autoantibodies neutralizing type I IFNs underlie West Nile virus encephalitis in ∼40% of patients. J Exp Med. 2023 Sep 4;220(9):e20230661. doi: 10.1084/jem.20230661. PMID: 37347462
- Platform to systematically recruit and collect samples from selected patients and cohorts
- Exome and genome sequencing data processing and analysis
- Screening for neutralizing anti-cytokine auto-antibodies
- Genome-wide genotyping data processing and genome-wide association study (GWAS)
- Human genomics of group B streptococcal colonization and infection’ (RC2019)
- Human genomics of group B streptococcal serology in pregnancy’ (5X1000)
- Genomica umana della colonizzazione delle donne gravide da parte di Streptococco di gruppo B’ (Fondazione UniCredit)
- Anti-interferon type I auto-antibodies and inborn errors of immunity in patients with life-threatening viral infection’ (RC2022)
- Tackling viral infections and autoimmunity through diagnosis, screening and investigation of single-gene inborn errors of immunity and auto-Abs neutralizing type I interferons’ (VISIONS, RF-2024-12377957)
We take advantage of our strategic position, at the crossroads between science and clinical work, to collaborate with clinical wards and research groups worldwide. Our main collaborations with research groups include:
- The CovidHGE consortium (www.covidhge.com)
- The Casanova lab (Laboratory of Human Genetics of Infectious Diseases, HGID), UT Southwestern Medical Center, Dallas, TX, USA, and Institut Imagine, Paris, France, EU
- The Fellay lab, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland
- The Geneva Centre for Inflammation Research (GCIR), University of Geneva, Geneva, Switzerland
GROUP MEMBERS:
Francesca Trespidi, Micol Angelini, Cristian Achille, Francesca Garofoli.
Dott. Borghesi Alessandro
Ultimo aggiornamento: 13/10/2026
