A TLR4 agonist liposome formulation effectively stimulates innate immunity and enhances protection from bacterial infection

Author:

Hedges Jodi F.1ORCID,Snyder Deann T.1,Robison Amanda1,Thompson Macy A.1,Aspelin Klara1,Plewa Jack1,Baldridge Jory2,Jutila Mark A.1

Affiliation:

1. Department of Microbiology and Cell Biology, Montana State University, P.O. Box 173610, Bozeman, MT, USA

2. Totem BioSciences, 240 Old Corvallis Road, Hamilton, MT 59840, USA

Abstract

Stimulation of innate immunity can protect against infectious insult and could be used in combination with other therapies. Since antibiotic resistance is an increasing concern, strategies to reduce the dose or eliminate the need for these drugs are warranted. Lipo-CRX is a formulation in which the TLR4 agonist CRX-527 is incorporated into lipid membranes in liposomes. Lipo-CRX is less inflammatory than either CRX-527 or LPS, but retains unique capacity to enhance host defense responses. We compared lipo-CRX to other agonists in vitro using mammalian cells and in vivo in mice, and assessed indicators of innate immune responses and protection from bacterial infection. Lipo-CRX is similar to E. coli LPS in its capacity to activate bovine γδ T cells and to recruit neutrophils into mouse lungs, but with less reactivity in the LAL assay. However, lipo-CRX uniquely induced the production of systemic innate immune cytokines. In the mouse model of brucellosis, delivery of lipo-CRX to the lungs reduced the dissemination of B. abortus. While lipo-CRX or the antibiotic ampicillin alone did not alter B. abortus burdens in the lung, the combination had a synergistic beneficial effect. Our data suggest that stimulating the innate immune system with lipo-CRX, either alone or when combined with antibiotics, can enhance bacterial clearance in the mouse model of brucellosis.

Funder

National Institute of Food and Agriculture

National Institute of Allergy and Infectious Diseases

Montana Agricultural Experiment Station

Publisher

SAGE Publications

Subject

Infectious Diseases,Cell Biology,Molecular Biology,Immunology,Microbiology

Cited by 2 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. Brucella infection and Toll-like receptors;Frontiers in Cellular and Infection Microbiology;2024-03-12

2. Innovative Phospholipid Carriers: A Viable Strategy to Counteract Antimicrobial Resistance;International Journal of Molecular Sciences;2023-11-03

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