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Newly Discovered Immune System Mechanism Suppresses Parasitic Infection

Pedro H. Gazzinelli Guimaraes, Ph.D.

Education:

Ph.D., 2014, Federal University of Minas Gerais, Brazil

M.S., 2010, Federal University of Minas Gerais, Brazil

Photo of Pedro H. Gazzinelli Guimaraes

Sasisekhar Bennuru, Ph.D.

Education:

Ph.D., 2005, Anna University, India

Sasisekhar Bennuru, Ph.D.

P’ng Loke Ph.D.

Education:

Ph.D., 2001, University of Edinburgh, UK

Headshot of P'ng Loke

Finding the Achilles' Heel of a Killer Parasite

Media Type
Article
Publish or Event Date
Research Institution
University of Texas Southwestern
Short Title
Finding the Achilles' Heel of a Killer Parasite
Content Coordinator
Content Manager

Pedro H. Gazzinelli Guimaraes, Ph.D.

Staff Scientist, Helminth Immunology Section

Major Areas of Research

  • Interaction between allergen- and helminth-driven type-2 immune responses
  • Biomarkers for helminth antigens- and allergens-specific human Th2 cells subsets
  • Multiomic profiling and TCR repertoire diversity of effector Th2 cells in the context of allergic diseases and helminth infections in both human studies and experimental models
  • Mechanisms of type-2 immune response induced by helminth infection and allergic sensitization in the lung tissue of experimental models
  • Influence of helminth infections on the regulation of the immune response of allergic individuals

Program Description

Dr. Gazzinelli-Guimaraes’ research program has been focused on the regulation of the immune response to helminth parasitic infections and to the pathogenesis of allergic diseases. 
We have a  specific interest in understanding the plasticity and specificity of circulating peripheral and tissue-resident effector Th2 cells driven by helminth antigens and/or allergens, as well as to understand the role of the effector Th2 subsets in the establishment of tissue Type-2-mediated inflammation using both mouse models and human studies. These studies aim to identify potential targets for the development of selective immunotherapy that could prevent chronic helminth infection or that could diminish allergic inflammation.

Biography

Dr. Gazzinelli Guimaraes received his master’s degree in Parasitology in 2010 from the Federal University of Minas Gerais, Brazil, and received his Ph.D. in 2014 from the same university. This was followed by a consulting training at the Schistosomiasis Control Initiative (SCI) based at Imperial College - London, UK in 2015, where he then became the supervisor of the Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) project in Cabo Delgado, Mozambique, managed by the University of Georgia–USA. He joined NIH in 2016 as a post-doctoral research fellow with Dr. Thomas Nutman in the Laboratory of Parasitic Diseases (LPD), NIAID. He is currently a Staff Scientist in LPD.

Publications

Kupritz J, Angelova A, Nutman TB, Gazzinelli-Guimaraes PH. Helminth-Induced Human Gastrointestinal Dysbiosis: a Systematic Review and Meta-Analysis Reveals Insights into Altered Taxon Diversity and Microbial Gradient Collapse. mBio. 2021 Dec 21;12(6):e0289021.

Gazzinelli-Guimaraes PH, Bennuru S, de Queiroz Prado R, Ricciardi A, Sciurba J, Kupritz J, Moser M, Kamenyeva O, Nutman TB. House dust mite sensitization drives cross-reactive immune responses to homologous helminth proteins. PLoS Pathog. 2021 Mar 2;17(3):e1009337.

Gazzinelli-Guimaraes PH, de Queiroz Prado R, Ricciardi A, Bonne-Année S, Sciurba J, Karmele EP, Fujiwara RT, Nutman TB. Allergen presensitization drives an eosinophil-dependent arrest in lung-specific helminth development. J Clin Invest. 2019 Aug 5;129(9):3686-3701.

Lee SH, Chaves MM, Kamenyeva O, Gazzinelli-Guimaraes PH, Kang B, Pessenda G, Passelli K, Tacchini-Cottier F, Kabat J, Jacobsen EA, Nutman TB, Sacks DL. M2-like, dermal macrophages are maintained via IL-4/CCL24-mediated cooperative interaction with eosinophils in cutaneous leishmaniasis. Sci Immunol. 2020 Apr 10;5(46):eaaz4415.

Gazzinelli-Guimarães PH, Bonne-Année S, Fujiwara RT, Santiago HC, Nutman TB. Allergic Sensitization Underlies Hyperreactive Antigen-Specific CD4+ T Cell Responses in Coincident Filarial Infection. J Immunol. 2016 Oct 1;197(7):2772-9. doi: 10.4049/jimmunol.1600829. Epub 2016 Aug 26. PMID: 27566825; PMCID: PMC5026971.

Gazzinelli-Guimaraes PH, Nutman TB. Helminth parasites and immune regulation. F1000Res. 2018 Oct 23;7:F1000 Faculty Rev-1685.

Visit PubMed for a complete publication listing.

Section or Unit Name
Helminth Immunology Section
First Name
Pedro
Last Name
Gazzinelli Guimaraes
Exclude from directory
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Section/Unit: Location
This Researcher/Clinician’s Person Page
Program Description

Dr. Gazzinelli-Guimaraes’ research program has been focused on the regulation of the immune response to helminth parasitic infections and to the pathogenesis of allergic diseases. 
We have a  specific interest in understanding the plasticity and specificity of circulating peripheral and tissue-resident effector Th2 cells driven by helminth antigens and/or allergens, as well as to understand the role of the effector Th2 subsets in the establishment of tissue Type-2-mediated inflammation using both mouse models and human studies. These studies aim to identify potential targets for the development of selective immunotherapy that could prevent chronic helminth infection or that could diminish allergic inflammation.

Selected Publications

Kupritz J, Angelova A, Nutman TB, Gazzinelli-Guimaraes PH. Helminth-Induced Human Gastrointestinal Dysbiosis: a Systematic Review and Meta-Analysis Reveals Insights into Altered Taxon Diversity and Microbial Gradient Collapse. mBio. 2021 Dec 21;12(6):e0289021.

Gazzinelli-Guimaraes PH, Bennuru S, de Queiroz Prado R, Ricciardi A, Sciurba J, Kupritz J, Moser M, Kamenyeva O, Nutman TB. House dust mite sensitization drives cross-reactive immune responses to homologous helminth proteins. PLoS Pathog. 2021 Mar 2;17(3):e1009337.

Gazzinelli-Guimaraes PH, de Queiroz Prado R, Ricciardi A, Bonne-Année S, Sciurba J, Karmele EP, Fujiwara RT, Nutman TB. Allergen presensitization drives an eosinophil-dependent arrest in lung-specific helminth development. J Clin Invest. 2019 Aug 5;129(9):3686-3701.

Lee SH, Chaves MM, Kamenyeva O, Gazzinelli-Guimaraes PH, Kang B, Pessenda G, Passelli K, Tacchini-Cottier F, Kabat J, Jacobsen EA, Nutman TB, Sacks DL. M2-like, dermal macrophages are maintained via IL-4/CCL24-mediated cooperative interaction with eosinophils in cutaneous leishmaniasis. Sci Immunol. 2020 Apr 10;5(46):eaaz4415.

Gazzinelli-Guimarães PH, Bonne-Année S, Fujiwara RT, Santiago HC, Nutman TB. Allergic Sensitization Underlies Hyperreactive Antigen-Specific CD4+ T Cell Responses in Coincident Filarial Infection. J Immunol. 2016 Oct 1;197(7):2772-9. doi: 10.4049/jimmunol.1600829. Epub 2016 Aug 26. PMID: 27566825; PMCID: PMC5026971.

Gazzinelli-Guimaraes PH, Nutman TB. Helminth parasites and immune regulation. F1000Res. 2018 Oct 23;7:F1000 Faculty Rev-1685.

Visit PubMed for a complete publication listing.

Major Areas of Research
  • Interaction between allergen- and helminth-driven type-2 immune responses
  • Biomarkers for helminth antigens- and allergens-specific human Th2 cells subsets
  • Multiomic profiling and TCR repertoire diversity of effector Th2 cells in the context of allergic diseases and helminth infections in both human studies and experimental models
  • Mechanisms of type-2 immune response induced by helminth infection and allergic sensitization in the lung tissue of experimental models
  • Influence of helminth infections on the regulation of the immune response of allergic individuals

Supporting Research to Reduce the Burden of Neglected Tropical Diseases

NIAID Now |

January 30, 2022, marks the third World Neglected Tropical Diseases (NTDs) Day, presenting an opportunity to reflect both on the continuing burden imposed by these diseases and the significant progress made to curtail them. NTDs comprise viral, bacterial, fungal and parasitic diseases that, despite their various causes, have in common their substantial health, social and economic impacts, especially on marginalized populations living in tropical and subtropical countries.

Despite substantial progress in controlling NTDs in the past decade, these conditions still affect more than 1 billion people worldwide (WHO NTD Roadmap 2021-2030). Although NTDs do not typically cause death, they impede affected individuals’ ability to lead healthy lives, and reduce their growth and development, educational attainment and economic productivity. They also result in stigmatization and social inequities.   Consequently, NTDs contribute to a self-perpetuating cycle of illness leading to decreased human, social and economic development, which in turn fosters persistence of NTDs.

To break the cycle, new and improved interventions as well as effective implementation are needed. As part of its efforts to address global health, NIAID has long supported research and development to better understand, diagnose, treat and prevent NTDs. 

In these video interviews, NIAID staff highlight activities and advances that the Institute has supported as part of its collaborative work with partners around the world aimed at lifting the burden of NTDs.

Contact Information

Contact the NIAID Media Team.

301-402-1663
niaidnews@niaid.nih.gov

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Sasisekhar Bennuru, Ph.D.

Associate Scientist, Helminth Immunology Section

Major Areas of Research

  • Molecular characterization of helminth parasites with a focus on filarial infections
  • Development of diagnostics and biomarker discovery for helminth infections
  • Host-parasite interactions towards defining pathogenesis of filarial infection

Biography

Dr. Bennuru received his Ph.D in 2005 from the Center for Biotechnology, Anna University in Chennai, India. He joined NIH in 2005 as a post-doctoral research fellow with Dr. Thomas Nutman in the Laboratory of Parasitic Diseases, primarily working on cellular and molecular aspects of human filarial infections and has been a staff scientist since 2013.

Program Description

Dr. Bennuru’s research focus within the Helminth Immunology Section is a multi-omic approach to understand the biology of parasitic helminths (especially human filarial infections, e.g., lymphatic filariasis, onchocerciasis, and loiasis) and the host-parasite interaction toward defining pathogenesis; to identify parasite-encoded therapeutic, diagnostic, and vaccine-related targets; and to develop biomarkers of species-specific filarial infection.

Publications

Ricciardi A, Bennuru S, Tariq S, Kaur S, Wu W, Elkahloun AG, Arakelyan A, Shaik J, Dorward DW, Nutman TB, Tolouei Semnani R. Extracellular vesicles released from the filarial parasite Brugia malayi downregulate the host mTOR pathway. PLoS Negl Trop Dis. 2021 Jan;15(1):e0008884.

Easton A, Gao S, Lawton SP, Bennuru S, Khan A, Dahlstrom E, Oliveira RG, Kepha S, Porcella SF, Webster J, Anderson R, Grigg ME, Davis RE, Wang J, Nutman TB. Molecular evidence of hybridization between pig and human Ascaris indicates an interbred species complex infecting humans. Elife. 2020 Nov;9:e61562.

Bennuru S, Oduro-Boateng G, Osigwe C, Del Valle P, Golden A, Ogawa GM, Cama V, Lustigman S, Nutman TB. Integrating Multiple Biomarkers to Increase Sensitivity for the Detection of Onchocerca volvulus Infection. J Infect Dis. 2020 May;221(11):1805-1815.

Bennuru S, Cotton JA, Ribeiro JM, Grote A, Harsha B, Holroyd N, Mhashilkar A, Molina DM, Randall AZ, Shandling AD, Unnasch TR, Ghedin E, Berriman M, Lustigman S, Nutman TB. Stage-Specific Transcriptome and Proteome Analyses of the Filarial Parasite Onchocerca volvulus and Its Wolbachia Endosymbiont. mBio. 2016 Nov;7(6):e02028-16.

Cotton JA, Bennuru S, Grote A, Harsha B, Tracey A, Beech R, Doyle SR, Dunn M, Hotopp JC, Holroyd N, Kikuchi T, Lambert O, Mhashilkar A, Mutowo P, Nursimulu N, Ribeiro JM, Rogers MB, Stanley E, Swapna LS, Tsai IJ, Unnasch TR, Voronin D, Parkinson J, Nutman TB, Ghedin E, Berriman M, Lustigman S. The genome of Onchocerca volvulus, agent of river blindness. Nat Microbiol. 2016 Nov;2:16216.

D'Ambrosio MV, Bakalar M, Bennuru S, Reber C, Skandarajah A, Nilsson L, Switz N, Kamgno J, Pion S, Boussinesq M, Nutman TB, Fletcher DA. Point-of-care quantification of blood-borne filarial parasites with a mobile phone microscope. Sci Transl Med. 2015 May;7(286):286re4.

Visit PubMed for a complete publication listing.

Patents

Nutman TB, Bennuru S, Drame PM, inventors; The Unites States of America as represented by the Department of Health and Human Services, assignee. Compositions and methods for detecting Loa loa. United States patent US 10,598,655. 24 March 2020.

Mitre EE, Morris C, Bennuru S, Nutman T, inventors; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., The Unites States of America as represented by the Department of Health and Human Services, assignee. Immunogenic compositions and vaccines for preventing or treating filarial disease. United States patent US 10,441,642. 15 Oct 2019.

Section or Unit Name
Helminth Immunology Section
First Name
Sasisekhar
Last Name
Bennuru
Suffix
Ph.D.
Exclude from directory
Off
Section/Unit: Location
This Researcher/Clinician’s Person Page
Program Description

Dr. Bennuru’s research focus within the Helminth Immunology Section is a multi-omic approach to understand the biology of parasitic helminths (especially human filarial infections, e.g., lymphatic filariasis, onchocerciasis, and loiasis) and the host-parasite interaction toward defining pathogenesis; to identify parasite-encoded therapeutic, diagnostic, and vaccine-related targets; and to develop biomarkers of species-specific filarial infection.

Selected Publications

Gazzinelli-Guimaraes PH, Bennuru S, de Queiroz Prado R, Ricciardi A, Sciurba J, Kupritz J, Moser M, Kamenyeva O, Nutman TB. House dust mite sensitization drives cross-reactive immune responses to hologous helminth proteins. PLoS Pathog. 2021 Mar 2;17(3):e1009337.

Easton A, Gao S, Lawton SP, Bennuru S, Khan A, Dahlstrom E, Oliveira RG, Kepha S, Porcella SF, Webster J, Anderson R, Grigg ME, Davis RE, Wang J, Nutman TB. Molecular evidence of hybridization between pig and human Ascaris indicates an interbred species complex infecting humans. Elife. 2020 Nov;9:e61562.

Bennuru S, Oduro-Boateng G, Osigwe C, Del Valle P, Golden A, Ogawa GM, Cama V, Lustigman S, Nutman TB. Integrating Multiple Biomarkers to Increase Sensitivity for the Detection of Onchocerca volvulus Infection. J Infect Dis. 2020 May;221(11):1805-1815.

Bennuru S, Cotton JA, Ribeiro JM, Grote A, Harsha B, Holroyd N, Mhashilkar A, Molina DM, Randall AZ, Shandling AD, Unnasch TR, Ghedin E, Berriman M, Lustigman S, Nutman TB. Stage-Specific Transcriptome and Proteome Analyses of the Filarial Parasite Onchocerca volvulus and Its Wolbachia Endosymbiont. mBio. 2016 Nov;7(6):e02028-16.

Cotton JA, Bennuru S, Grote A, Harsha B, Tracey A, Beech R, Doyle SR, Dunn M, Hotopp JC, Holroyd N, Kikuchi T, Lambert O, Mhashilkar A, Mutowo P, Nursimulu N, Ribeiro JM, Rogers MB, Stanley E, Swapna LS, Tsai IJ, Unnasch TR, Voronin D, Parkinson J, Nutman TB, Ghedin E, Berriman M, Lustigman S. The genome of Onchocerca volvulus, agent of river blindness. Nat Microbiol. 2016 Nov;2:16216.

D'Ambrosio MV, Bakalar M, Bennuru S, Reber C, Skandarajah A, Nilsson L, Switz N, Kamgno J, Pion S, Boussinesq M, Nutman TB, Fletcher DA. Point-of-care quantification of blood-borne filarial parasites with a mobile phone microscope. Sci Transl Med. 2015 May;7(286):286re4.

Visit PubMed for a complete publication listing.

Additional Information

Patents

Nutman TB, Bennuru S, Drame PM, inventors; The Unites States of America as represented by the Department of Health and Human Services, assignee. Compositions and methods for detecting Loa loa. United States patent US 10,598,655. 24 March 2020.

Mitre EE, Morris C, Bennuru S, Nutman T, inventors; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., The Unites States of America as represented by the Department of Health and Human Services, assignee. Immunogenic compositions and vaccines for preventing or treating filarial disease. United States patent US 10,441,642. 15 Oct 2019.

Visit the U.S. Patent and Trademark Office for a complete patent listing.

Major Areas of Research
  • Molecular characterization of helminth parasites with a focus on filarial infections
  • Development of diagnostics and biomarker discovery for helminth infections
  • Host-parasite interactions towards defining pathogenesis of filarial infection

Schistosomiasis Research in Endemic Regions