NOD-scid IL2rγnull mice lacking TLR4 support human immune system development and the study of human-specific innate immunity

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 lac...

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Bibliographic Details
Published in:Journal of leukocyte biology 2023-05, Vol.113 (5), p.418-433
Main Authors: Aryee, Ken-Edwin, Shultz, Leonard D, Burzenski, Lisa M, Greiner, Dale L, Brehm, Michael A
Format: Article
Language:English
Subjects:
Animals
Humans
Immunity, Innate
Inflammation
Mice
Mice, Inbred NOD
Mice, SCID
Severe Combined Immunodeficiency
Toll-Like Receptor 4 - genetics
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Summary: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.
ISSN:1938-3673
1938-3673
DOI:10.1093/jleuko/qiac020