1) During my doctoral research in Parasitology at the Biological Sciences Institute (ICB) of the Federal University of Minas Gerais – UFMG, Brazil, under the guidance of Dr. Ricardo Fujiwara, I established and standardized experimental models for studying helminth parasites. These models allowed for the characterization of both parasitological and immunological aspects of early events occurring in helminth infections, which are challenging to investigate directly in humans within endemic areas. Our developed models not only deepened our understanding of the mechanisms driving lung-specific Type-2 responses induced by migrating helminth larvae but also revealed striking similarities with pulmonary allergic inflammation. Additionally, we investigated the potential interactions between lung-stage helminths and pulmonary viral infections, uncovering evidence that helminth infections can influence virus-specific responses at the tissue level.
- Gazzinelli-Guimaraes PH, de Freitas LF, Gazzinelli-Guimarães AC, Coelho F, Barbosa FS, Nogueira D, Amorim C, Dhom-Lemos LC, Oliveira LM, da Silveira AB, da Fonseca FG, Bueno LL, Fujiwara RT. Concomitant helminth infection downmodulates the Vaccinia virus-specific immune response and potentiates virus-associated pathology. International Journal for Parasitology. 2016.
- Nogueira DS*, Gazzinelli-Guimaraes PH*, Barbosa FS, Resende NM, Silva CC, de Oliveira LM, Amorim CC, Oliveira FM, Mattos MS, Kraemer LR, Caliari MV, Gaze S, Bueno LL, Russo RC, Fujiwara RT. Multiple Exposures to Ascaris suum Induce Tissue Injury and Mixed Th2/Th17 Immune Response in Mice. PLoS Neglected Tropical Diseases. 2016. *Authors contributed equally.
- Gazzinelli-Guimaraes PH, Gazzinelli-Guimarães AC, Silva FN, Mati VL, Dhom-Lemos L, Barbosa FS, Passos LS, Gaze S, Carneiro CM, Bartholomeu DC, Bueno LL, Fujiwara RT. Parasitological and immunological aspects of early Ascaris spp. infection in mice. International Journal for Parasitology. 2013.
- Gazzinelli-Guimaraes PH, Souza-Fagundes EM, Cancado GG, Martins VG, Dhom-Lemos LC, Ricci ND, Fiuza JA, Bueno LL, Miranda RR, Guatimosim S, Gazzinelli A, Correa-Oliveira R, Bartholomeu DC, Fujiwara RT. Cell apoptosis induced by hookworm antigens: a strategy of immunomodulation. Frontiers in Bioscience. 2013.
2) After completing my PhD, I assumed the role of consultant and coordinator for the SCORE (Schistosomiasis Consortium for Operational Research and Evaluation) project in Mozambique. My primary responsibility was to oversee a longitudinal study spanning multiple African countries, aimed at optimizing preventive chemotherapy strategies with praziquantel (PZQ) for controlling schistosomiasis. This involved evaluating the impact of various treatment approaches. In Mozambique, following the successful implementation of a mass administration program that treated over 300,000 individuals, I embarked on a trek through 150 villages to conduct parasitological surveys. These surveys entailed the collection of stool and urine samples from children. In summary, our extensive study revealed a significant reduction in the prevalence of urogenital schistosomiasis among adults across the different treatment arms tested. This suggests a decrease in the transmission rate within the community, even in instances where only school children received treatment. These findings have profound logistical and cost-saving implications for national control programs, particularly in justifying the implementation of community-wide treatment strategies.
- Gazzinelli-Guimaraes PH, Dhanani N, King CH, Campbell CH, Aurelio HO, Ferro J, Nala R, Fenwick A,Phillips AE. Accuracy of the WHO praziquantel dose pole for large-scale community treatment of urogenital schistosomiasis in northern Mozambique: Is it time for an update? PLoS Neglected Tropical Diseases. 2018. doi: 10.1371/journal.pntd.0006957
- Binder S, Campbell CH, Castleman JD, Kittur N, Kinung'hi S, Olsen A, Magnussen P, Karanja DMS, Mwinzi PNM, Montgomery SP, Secor WE, Phillips AE, Dhanani N, Gazzinelli-Guimaraes PH, Clements M, N'Goran EK, Meite A, Utzinger J, Hamidou AA, Garba A, Fleming FM, Whalen CC, King CH, Colley DG. Lessons Learned in Conducting Mass Drug Administration for Schistosomiasis Control and Measuring Coverage in an Operational Research Setting. American Journal of Tropical Medicine and Hygiene. 2020.
- King CH, Kittur N, Binder S, Campbell CH, N'Goran EK, Meite A, Utzinger J, Olsen A, Magnussen P, Kinung'hi S, Fenwick A, Phillips AE, Gazzinelli-Guimaraes PH, Dhanani N, Ferro J, Karanja DMS, Mwinzi PNM, Montgomery SP, Wiegand RE, Secor WE, Hamidou AA, Garba A, Colley DG. Impact of Different Mass Drug Administration Strategies for Gaining and Sustaining Control of Schistosoma mansoni and Schistosoma haematobium Infection in Africa. American Journal of Tropical Medicine and Hygiene. 2020.
- Phillips AE, Gazzinelli-Guimaraes PH, Aurelio HO, Dhanani N, Ferro J, Nala R, Deol A, Fenwick A. Urogenital schistosomiasis in Cabo Delgado, northern Mozambique: baseline findings from the SCORE study. Parasite and Vectors. 2018.
- Phillips AE, Gazzinelli-Guimaraes PH, Aurelio HO, Ferro J, Nala R, Clements M, King CH, Fenwick A, Fleming FM, Dhanani N. Assessing the benefits of five years of different approaches to treatment of urogenital schistosomiasis: A SCORE project in Northern Mozambique. PLoS Neglected Tropical Diseases. 2017.
3) More recently, I developed a translational research platform from basic science in experimental models to a comprehensive study in humans to interrogate the molecular basis and pathogenesis of the allergen- and helminth parasite-driven effector type-2 inflammation. These studies have been helping us to identify potential targets for the development of selective immunotherapy that could prevent chronic helminth infection or that could diminish allergic inflammation. In an early project published as the first author in the Journal of Immunology in 2016, we showed that Th2 responses to helminth antigens are augmented in helminth infected individuals with concomitant common allergies. We showed helminth parasite antigens induced a marked increase in the frequencies of a circulating polyfunctional Th2 CD4+IL-2+IL-4+IL-5+TNF-a+ T cells in the PBMCs of the group of house dust mite (HDM) allergic individuals concomitantly infected with filarial parasites when compared to non-allergic but helminth-infected patients. This work was followed by an important publication in the Journal of Clinical Investigation (Gazzinelli-Guimaraes et al., 2019, first author) demonstrating in a murine model of house dust mite (HDM)-induced allergic inflammation, that pre-existing allergen sensitization markedly control Ascaris larval development. We further showed that in this model larval killing was driven by an eosinophil-dependent pulmonary type-2-immune response. In an important study published in Plos Pathogens (Gazzinelli-Guimaraes et al., 2021, first author), we demonstrated antibody cross-reactions between an allergen (house dust mite) and helminths thus providing a potential explanation for this allergy-helminth interaction. More recently, we interrogated the immunological underpinnings of this allergen-driven eosinophil-dominated type-2 inflammation, by investigating the upstream mechanisms of the effector pathogenesis of the allergic pulmonary diseases. Some of the major findings from this project has been published recently in the Journal of Allergy and Clinical Immunology: Global (Gazzinelli-Guimaraes et al., 2023, first author), which demonstrates that the eosinophil trafficking to the allergic lung relies on IL-13 driven CCL- 11/CCL-24 production by fibroblasts and myeloid cells, respectively, in response to HDM allergen sensitization.
- Gazzinelli-Guimaraes PH, Dulek B, Swanson P, Lack J, Roederer M, Nutman TB. Single-cell molecular signature of pathogenic T helper subsets in type 2-associated disorders in humans. JCI Insight. 2024 Apr 8;9(7):e177720.
- Gazzinelli-Guimaraes PH, Golec D, Karmele EP, Sciurba J, Bara-Garcia P, Hill T, Kang B, Bennuru S, Schwartzberg P, Nutman T. Eosinophil trafficking to the allergic lung relies on IL-13 driven CCL-11/CCL-24 production by fibroblasts/myeloid cells. Journal of Allergy and Clinical Immunology: Global. 2023.
- Gazzinelli-Guimaraes PH, Bennuru S, Prado R, Ricciardi A, Sciurba J, Moser M, Kamanyeva O, Nutman T. House dust mite sensitization drives cross-reactive immune responses to homologous helminth proteins. Plos Pathogens. 2021.
- Gazzinelli-Guimaraes PH, Prado; R, Ricciardi, A; Bonne-Année S, Sciurba J, Karmele E, Fujiwara R, Nutman T. Allergen pre-sensitization drives an eosinophil-dependent arrest in lung-specific helminth development. Journal of Clinical Investigation. 2019
- Gazzinelli-Guimaraes PH, Nutman TB. Helminth parasites and immune regulation. F1000Reviews. 2018.
- Gazzinelli-Guimaraes PH, Bonne-Année S, Fujiwara RT, Santiago HC, Nutman TB. Allergic Sensitization Underlies Hyperreactive Antigen-Specific CD4+ T Cell Responses in Coincident Filarial Infection. Journal of Immunology. 2016.
4) As a mentor in the lab, I have been training post-bacs, Masters’, and PhD students. Recently, an interesting study published in mBio by one of my students (Kupritz et al., 2021), we demonstrated that helminth-induced human gastrointestinal dysbiosis appears to be specific to soil-transmitted helminths (STH) species and host anatomical niche, which lead to relevant implications into the pathogen-host interaction, and shed new lights into the understanding on how helminth parasites influence the host microbiome. In addition, a study published by Dr. Lopes, a former PhD student in my lab, demonstrated by the first time a pathogenic role for NOD1 signaling in Ascaris-driven pulmonary tissue inflammation, with downstream implications in hematopoietic cell recruitment and inflammatory cascades linked to the host innate immune responses.
- Lopes CA, Wang J, Liffner B, Absalon S, Gazzinelli-Guimaraes PH. Ascaris Mouse Model Protocols: Advancing Research on Larval Ascariasis Biology. Current Protocols. 2024.
- Kupritz, J, Angelova A, Nutman T, Gazzinelli-Guimaraes PH. Helminth-induced human gastrointestinal dysbiosis: a systematic review and meta-analysis reveals insights into altered taxa diversity and microbial gradient collapse. mBio. 2021.