Current Investigators

Christopher A. Hunter, PhD

  • LaptopsChristopher 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

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

R01 AI157247-02 Hunter/ Koshy MPI 09/23/20-08/31/25
NIAID
Neuronal Latency and Toxoplasma

U01 AI160664 Kedl PI/Hunter Co-PI 03/25/21-02/28/26
NIAID
Mechanisms of combined CD40/TLR adjuvant-elicited cellular immunity

U01 AI163671-02 Hunter/ Striepen MPI 06/01/21-05/31/26
NIAID
The role of CD40L in resistance to enteric infection

Janssen R&D (66253) Hunter PI 09/13/21-09/13/23
Janssen
Impact of IL-27 treatment on immunity to Toxoplasma

Publications

Christopher A. Hunter, Ph.D.

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

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Current Investigators