Christopher A. Hunter, PhD
Christopher A. Hunter, PhD
Mindy Halikman Heyer Distinguished Professor of Pathobiology
University of Pennsylvania
School of Veterinary Medicine
Room 310F Hill Pavilion
380 South University Av
Philadelphia, PA 19104-4539- Phone: 215-573-7772
- Fax: 215-746-2295
- Email: chunter@vet.upenn.edu
- Web: vet.upenn.edu
MIST Research
The ability of recently activated T cells to express the cell surface molecule CD40L allows them to communicate with other immune and non-immune populations. This molecule is of particular importance in the gut to help control the parasitic infection caused by Cryptosporidium. Here we leverage a novel, natural mouse model of Cryptosporidium to dissect the impact of the CD40-CD40L interaction in T cell-mediated resistance to infection in the gut. In this model, WT mice (like humans) develop sterile immunity mediated by T cell production of IFN-, but mice that lack CD40L mice (like humans) do not resolve infection. In addition, treatment of chronically infected CD40L-deficient mice with soluble (s)CD40L results in rapid parasite clearance. We will test if protective effect of CD40L may be explained by either I. its ability to promote T cell responses essential for resistance and/or II. because CD40L directly activates EC to limit parasite growth. We are uniquely equipped to utilize parasite transgenesis, combined with sophisticated genetic approaches to define the key cellular interactions that allows CD40L to determine the outcome of an enteric infection.
Current Grant Support
| 1R01AI148249-03 | Striepen/ Hunter MPI | 12/01/19-11/30/24 |
| NIAID Immunity to Cryptosporidium |
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| Penn COVID 19 Pilot | Hunter PI | 06/01/20-11/30/22 |
| Penn The Role of IL-27 in Limiting the Development of Cytokine Storms |
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| R01 AI157247-02 | Hunter/ Koshy MPI | 09/23/20-08/31/25 |
| NIAID Neuronal Latency and Toxoplasma |
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| U01 AI160664 | Kedl PI/Hunter Co-PI | 03/25/21-02/28/26 |
| NIAID Mechanisms of combined CD40/TLR adjuvant-elicited cellular immunity |
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| U01 AI163671-02 | Hunter/ Striepen MPI | 06/01/21-05/31/26 |
| NIAID The role of CD40L in resistance to enteric infection |
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| Janssen R&D (66253) | Hunter PI | 09/13/21-09/13/23 |
| Janssen Impact of IL-27 treatment on immunity to Toxoplasma |
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Publications
Christopher A. Hunter, Ph.D.
Pardy, R. D. et al. Analysis of intestinal epithelial cell responses to Cryptosporidium highlights the temporal effects of IFN-gamma on parasite restriction. PLoS Pathog 20, e1011820 (2024).
Wallbank, B., Pardy, R. D., Brodsky, I. E., Hunter, C. A. & Striepen, B. Cryptosporidium impacts epithelial turnover and is resistant to induced cell death. mBio in press (2024).
Walzer, K. A. et al. Transcriptional control of the Cryptosporidium life cycle. Nature (2024).
Cohn, I. S., Henrickson, S. E., Striepen, B. & Hunter, C. A. Immunity to Cryptosporidium: Lessons from Acquired and Primary Immunodeficiencies. J Immunol 209, 2261-2268 (2022).
Cohn, I. S. et al. Intestinal cDC1s provide cues required for CD4+ T cell-mediated resistance to Cryptosporidium. J Exp Med 221 (2024).
Haskins, B. E. et al. Dendritic cell-mediated responses to secreted Cryptosporidium effectors promote parasite-specific CD8(+) T cell responses. Mucosal Immunol 17, 387-401 (2024).
Pardy, R. D., Wallbank, B. A., Striepen, B. & Hunter, C. A. Immunity to Cryptosporidium: insights into principles of enteric responses to infection. Nat Rev Immunol 24, 142-155 (2024).
Doke T, Abedini A, Aldridge DL, Yang YW, Park J, Hernandez CM, Balzer MS, Shrestra R, Coppock G, Rico JMI, Han SY, Kim J, Xin S, Piliponsky AM, Angelozzi M, Lefebvre V, Siracusa MC, Hunter CA, Susztak K. 2022. Single-cell analysis identifies the interaction of altered renal tubules with basophils orchestrating kidney fibrosis. Nat Immunol 23: 947-59
Gibson AR, Sateriale A, Dumaine JE, Engiles JB, Pardy RD, Gullicksrud JA, O'Dea KM, Doench JG, Beiting DP, Hunter CA, Striepen B. 2022. A genetic screen identifies a protective type III interferon response to Cryptosporidium that requires TLR3 dependent recognition. PLoS Pathog 18: e1010003
Christian DA, Adams TA, 2nd, Shallberg LA, Phan AT, Smith TE, Abraha M, Perry J, Ruthel G, Clark JT, Pritchard GH, Aronson LR, Gossa S, McGavern DB, Kedl RM, Hunter CA. 2022. cDC1 coordinate innate and adaptive responses in the omentum required for T cell priming and memory. Sci Immunol 7: eabq7432
Shallberg LA, Phan AT, Christian DA, Perry JA, Haskins BE, Beiting DP, Harris TH, Koshy AA, Hunter CA. 2022. Impact of secondary TCR engagement on the heterogeneity of pathogen-specific CD8+ T cell response during acute and chronic toxoplasmosis. PLoS Pathog 18: e1010296
Perry JA, Shallberg L, Clark JT, Gullicksrud JA, DeLong JH, Douglas BB, Hart AP, Lanzar Z, O'Dea K, Konradt C, Park J, Kuchroo JR, Grubaugh D, Zaretsky AG, Brodsky IE, Malefyt RD, Christian DA, Sharpe AH, Hunter CA. 2022. PD-L1-PD-1 interactions limit effector regulatory T cell populations at homeostasis and during infection. Nature Immunology 23: 743-+
Clark JT, Christian DA, Gullicksrud JA, Perry JA, Park J, Jacquet M, Tarrant JC, Radaelli E, Silver J, Hunter CA. 2021. IL-33 promotes innate lymphoid cell-dependent IFN-gamma production required for innate immunity to Toxoplasma gondii. Elife 10: doi: 10.7554/eLife.65614
Sateriale A, Gullicksrud JA, Engiles JB, McLeod BI, Kugler EM, Henao-Mejia J, Zhou T, Ring AM, Brodsky IE, Hunter CA, Striepen B. 2021. The intestinal parasite Cryptosporidium is controlled by an enterocyte intrinsic inflammasome that depends on NLRP6. Proc Natl Acad Sci U S A 118
Gullicksrud JA, Sateriale A, Engiles JB, Gibson AR, Shaw S, Hutchins ZA, Martin L, Christian DA, Taylor GA, Yamamoto M, Beiting DP, Striepen B, Hunter CA. 2021. Enterocyte-innate lymphoid cell crosstalk drives early IFN-gamma-mediated control of Cryptosporidium. Mucosal Immunol
Lam LKM, Murphy S, Kokkinaki D, Venosa A, Sherrill-Mix S, Casu C, Rivella S, Weiner A, Park J, Shin S, Vaughan AE, Hahn BH, Odom John AR, Meyer NJ, Hunter CA, Worthen GS, Mangalmurti NS. 2021. DNA binding to TLR9 expressed by red blood cells promotes innate immune activation and anemia. Sci Transl Med 13: eabj1008
Aldridge DL, Phan AT, de Waal Malefyt R, Hunter CA. 2021. Limited Impact of the Inhibitory Receptor TIGIT on NK and T Cell Responses during Toxoplasma gondii Infection. Immunohorizons 5: 384-94