NOD-scid IL2rγnull mice lacking TLR4 support human immune system development and the study of human-specific innate immunity.
Document Type
Article
Publication Date
5-2-2023
Original Citation
Aryee K,
Shultz LD,
Burzenski L,
Greiner D,
Brehm M.
NOD-scid IL2rγnull mice lacking TLR4 support human immune system development and the study of human-specific innate immunity. J Leukoc Biol. 2023;113(5):418-33.
Keywords
JMG, SS1, Animals, Humans, Mice, Immunity, Innate, Inflammation, Mice, Inbred NOD, Mice, SCID, Severe Combined Immunodeficiency, Toll-Like Receptor 4
JAX Source
J Leukoc Biol. 2023;113(5):418-33.
ISSN
1938-3673
PMID
36801998
DOI
https://doi.org/10.1093/jleuko/qiac020
Grant
This work was supported in part by the JDRF and the National Institutes of Health grants CA034196 (L.D.S.), AI132963 (M.A.B.L.D.S.), OD026440 (D.L.G., M.A.B., L.D.S.), and NIDDK-supported Human Islet Research Network (https://hirnetwork.org) DK104218.
Abstract
Agents that induce inflammation have been used since the 18th century for the treatment of cancer. The inflammation induced by agents such as Toll-like receptor agonists is thought to stimulate tumor-specific immunity in patients and augment control of tumor burden. While NOD-scid IL2rγnull mice lack murine adaptive immunity (T cells and B cells), these mice maintain a residual murine innate immune system that responds to Toll-like receptor agonists. Here we describe a novel NOD-scid IL2rγnull mouse lacking murine TLR4 that fails to respond to lipopolysaccharide. NSG-Tlr4null mice support human immune system engraftment and enable the study of human-specific responses to TLR4 agonists in the absence of the confounding effects of a murine response. Our data demonstrate that specific stimulation of TLR4 activates human innate immune systems and delays the growth kinetics of a human patient-derived xenograft melanoma tumor.