Human Immunobiology and Pathogenesis

Why do people respond so differently to the same infection or treatment? The human immune system is remarkably adaptable, shaped by our biology and the environments we live in. These differences help explain why some individuals are more vulnerable to infections or immune-related diseases than others. Yet, the mechanisms behind this immune variability remain poorly understood, limiting our ability to deliver tailored treatments.

We are addressing this challenge by studying how immune responses within human tissues are influenced not only by the local environment but also by intrinsic factors such as sex and age, as well as environmental exposures including temperature and micro- and nanoplastics. Our lab leads an ambitious, cross-disciplinary research program that brings together fundamental immunology and clinical research across a network of 10 hospitals, enabling rapid translation of discovery into patient-relevant insight. This includes training the next generation of clinician-scientists, by mentoring physicians pursuing PhDs that bridge clinical practice and translational research, working alongside BSc, MSc, and PhD fundamental researchers.
Our ultimate goal is medical translation: to define molecular mediators and immune effectors, identify predictive biomarkers, and design rigorously controlled clinical trials that enable precision medicine. Thus, advancing evidence-based immunotherapies that improve patient care.

Projects

Tackling infection through modulation of the hormonalimmune axis
This project explores how biological sex influences immune function and its changes with aging. By examining the interplay between hormones, aging, and immunity, we aim to uncover sex- and age-specific differences affecting respiratory infection outcomes and vaccine responses, providing insights into lifelong health disparities between males and females.
Funding: European Society for Clinical Microbiology and Infectious Diseases (ESCMID), granted on April 2023; Fundação para a Ciência e Tecnologia, granted on September 2025
Exploring the implications of sex differential immunity in Long COVID brain fog using neurospheroids
Long COVID disproportionately affects women, causing “brain fog,” yet underlying mechanisms remain unclear. Using a cohort of patients with persistent symptoms, we will map sex-specific immune responses, determine how differential cytokine profiles impair neuronal function in hiPSC-derived neurospheroids, and link effects to symptom severity, uncovering drivers of sex-biased Long COVID.
Funding: MPS-NOVA Exploratory project, granted in February 2025
AI-assisted spatial resolved thymic architecture in myasthenia gravis
We aim to decode myasthenia gravis by mapping thymic microenvironment changes driving pathogenic anti-AChR antibodies. Integrating 3D spatial transcriptomics, functional assays, and AI imaging, we will reveal abnormal cellular niches, identify biomarkers, and uncover mechanisms critical for curative therapies and in vitro MG models, enabling precision-targeted treatment development.
Funding: LS4 Future seed funding, 2nd edition, granted on April 2025
Thermal regulation of immune response in human lymphoid organs
Fever shapes immunity, yet its effects on human immune tissues remain poorly understood. Using pediatric tonsils, we will uncover how tonsillar immune cells reprogram effector functions in response to febrile temperatures. These insights uncover hyperthermia’s mechanistic role, guiding novel temperature-based strategies to modulate human immune responses.

Publications

Marcus Altfeld, Camila Consiglio, Darragh Duffy, Molly Ingersoll, Cliona O'Farrelly, Tal Pecht, Tal Shay, Helena Soares. The essential integration of sex and gender in immunological research. Immunology Letters 2025. DOI: 10.1016/j.imlet.2025.107097
José Feliz, Juliana Gonçalves, Carolina Cabedo, Maria Gamas, Maria Inês Neves, Helena SoaresLong-term sex differences in symptoms and immune profile in Long COVID. Preprint: Research Square 2025. DOI: 10.21203/rs.3.rs-7642874/v1
Gonçalves J, Melro M, Alenquer M, Araújo C, Castro-Neves J, Charepe N, Serrano F, Pontinha C, Amorim MJ, Soares H. Balance between maternal antiviral response and placental transfer of protection in gestational SARS-CoV-2 infection. JCI Insight 2023. 8(17):e167140, DOI: 10.1172/jci.insight.167140.
Gonçalves J, Juliano AM, Charepe N, Alenquer M, Athayde D, Ferreira F, Archer M, Amorim MJ, Serrano F, Soares H. Secretory IgA and T cells targeting SARS-CoV-2 spike protein are transferred to the breastmilk upon mRNA vaccination. Cell Rep Med 2021. 2. DOI: 10.1016/j.xcrm.2021.100468.
Amaral-Silva D, Gonçalves R, Torrão RC, Torres R, Pimentel-Santos F, Mourão AF, Costa M, Falcão S, Araújo MP, Gonçalves MJ, Lopes C, Neto A, Marona J, Costa T, Costa W, Branco JC, Soares H. Direct tissue sensing reprograms TLR4+ Tfh-like cells inflammatory profile in the joints of rheumatoid arthritis patients. Communications Biology 2021. 4:1135. DOI:10.1038/S42003-021-02659-0
Charepe N, Gonçalves J, Juliano AM, Lopes DG, Canhão H, Soares H, Serrano F. COVID-19 mRNA vaccine and antibody response in lactating women: a prospective cohort study, BMC Pregnancy and Childbirth 2021. 632. DOI: 10.1186/s12884-021-04051-6
Alenquer M, Ferreira F, Lousa D, Valério M, Medina-Lopes M, Bergman M-L, Gonçalves J, Demengeot J, Leite RB, Lilue J, Ning Z, Penha-Gonçalves C, Soares H, Soares CM, Amorim MJ. Signatures in SARS-CoV-2 spike protein conferring escape to neutralizing antibodies. PLOS Pathogens 2021. 17(8): e1009772. DOI: 10.1371/journal.ppar.1009772
Santos-Pereira A, Triunfante V, Araújo PMM, Martins J, Soares H, Poveda E, Souto B, Osório NS. Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil. Int. J. Mol. Sci. 2021. 22(10), 5304. DOI:10.3390/ijms22105304
Gonçalves J, Sousa RL, Jacinto MJ, Amaral-Silva D, Paula F, Sousa R, Zahedi S, Carvalho J, Cabral MG, Costa M, Branco JC, Canhão H, Alves JD, Rodrigues A, Soares H. Evaluating SARS-CoV-2 Seroconversion Following Relieve of Confinement Measures. Front Med 2020. DOI: 10.3389/fmed.2020.603996
Silva JG, Martins NP, Henriques R, Soares H. HIV-1 Nef Impairs the Formation of Calcium Membrane Territories Controlling the Signaling Nanoarchitecture at the Immunological Synapse. J. Immunol. 2016. 197: 4042 Highlighted in J Immunol November 15, 2016, 197 (10) 3749-3750. DOI: 10.4049/jimmunol.1601132

Prizes and Awards

2025 | Travel Award by Portuguese Immunology Society to Juliana Gonçalves (role: supervisor)
2023 | Best European Campaign Award granted conjointly by the International Union of Immunological Societies (IUIS) and by the European Federation of Immunological Societies (EFIS) to the vaccination campaign undertaken in
2021: “Conversations with Scientists: Decades of Research for Days of (COVID-19) Vaccines” Role; Core Organizer and Scientific Curator
2022 | Best Poster Award at the NovaHealth Conference to Júlia Castro-Neves (role: supervisor)
2022 | Travel Award by Portuguese Immunology Society to Daniela Amaral-Silva (role: supervisor)