Miles Tyner

All Publications

• Protective or pathogenic? Tuft cells shape divergent immune outcomes in helminth and viral infections. Current opinion in immunology Tyner, M. D., Howitt, M. R. 2025; 97: 102657

  Abstract

  Tuft cells are epithelial sentinels that monitor the luminal environment at barrier sites throughout the body. Their function as crucial initiators of type 2 immunity against helminths and protists in the intestine emerged nearly a decade ago. Since then, key tuft cell mechanisms and effectors involved in anti-helminth immunity have been described, but their responses to a wider array of microbes, like viruses, remain far less understood. Here, we review the roles of tuft cells during both helminth and viral infections at barrier tissues like the lung and the gut. While tuft cells protect against parasite infections, they exhibit a wider and sometimes contradictory influence on viral infections and pathology. We explore the emerging and context-dependent role of tuft cells in antiviral responses and examine how tuft cells act as molecular switches during helminth-viral co-infections to dramatically alter infection outcomes.

  View details for DOI 10.1016/j.coi.2025.102657

  View details for PubMedID 40945015

• Tuft cells mediate commensal remodeling of the small intestinal antimicrobial landscape. Proceedings of the National Academy of Sciences of the United States of America Fung, C., Fraser, L. M., Barrón, G. M., Gologorsky, M. B., Atkinson, S. N., Gerrick, E. R., Hayward, M., Ziegelbauer, J., Li, J. A., Nico, K. F., Tyner, M. D., DeSchepper, L. B., Pan, A., Salzman, N. H., Howitt, M. R. 2023; 120 (23): e2216908120

  Abstract

  Succinate produced by the commensal protist Tritrichomonas musculis (T. mu) stimulates chemosensory tuft cells, resulting in intestinal type 2 immunity. Tuft cells express the succinate receptor SUCNR1, yet this receptor does not mediate antihelminth immunity nor alter protist colonization. Here, we report that microbial-derived succinate increases Paneth cell numbers and profoundly alters the antimicrobial peptide (AMP) landscape in the small intestine. Succinate was sufficient to drive this epithelial remodeling, but not in mice lacking tuft cell chemosensory components required to detect this metabolite. Tuft cells respond to succinate by stimulating type 2 immunity, leading to interleukin-13-mediated epithelial and AMP expression changes. Moreover, type 2 immunity decreases the total number of mucosa-associated bacteria and alters the small intestinal microbiota composition. Finally, tuft cells can detect short-term bacterial dysbiosis that leads to a spike in luminal succinate levels and modulate AMP production in response. These findings demonstrate that a single metabolite produced by commensals can markedly shift the intestinal AMP profile and suggest that tuft cells utilize SUCNR1 and succinate sensing to modulate bacterial homeostasis.

  View details for DOI 10.1073/pnas.2216908120

  View details for PubMedID 37253002

• Succinate and tuft cells: how does this sensory process interface with food allergy? The Journal of allergy and clinical immunology Nico, K. F., Tyner, M. D., Howitt, M. R. 2022

  View details for DOI 10.1016/j.jaci.2022.07.016

  View details for PubMedID 35934085

• Comparing the effects of bisphenol A, C, and F on bovine theca cells in vitro REPRODUCTIVE TOXICOLOGY Tyner, M. D. W., Maloney, M. O., Kelley, B. J. B., Combelles, C. M. H. 2022; 111: 27-33

  Abstract

  Endocrine disrupting chemicals (EDCs) target aspects of hormone activity. Tightly coordinated crosstalk between two somatic cells of the ovary, granulosa and theca cells, governs steroid hormone production and plays a critical role in reproduction. It is thus pertinent to understand the impact of EDCs on granulosa and theca cells. Bisphenol A (BPA), a well-known EDC, is widely used in the manufacturing of consumer products with humans routinely exposed. Strong evidence of the adverse effects of BPA on the female reproductive system has emerged and as a result, manufacturers have begun replacing BPA with other bisphenols, such as BPC and BPF. The safety of these analogs is currently unclear and should be investigated independently. Although much is known about the impact of BPA on granulosa cells, similar study of theca cells has been neglected. Further, there is a lack of studies on the impact of BPC and BPF on the female reproductive system. To fill these gaps, the present study compared the effect of BPA, BPC, and BPF on the viability and steroid production of theca cells from bovine, a clinically relevant model for human reproduction. We show that BPC is more detrimental to theca cell viability and progesterone production compared to BPA. Surprisingly, we also found that BPF induces an increase in progesterone production compared to a decrease with BPA and BPC. To determine safety for the reproductive system, we conclude that a major shift away from BPA to bisphenol analogs should be investigated more thoroughly.

  View details for DOI 10.1016/j.reprotox.2022.05.003

  View details for Web of Science ID 000881513400002

  View details for PubMedID 35577017