Innate ImmunityPub Date : 2023-11-01Epub Date: 2023-10-13DOI: 10.1177/17534259231205993
Ahmet K Korkaya, Jeffrey Fischer, Anthony Peppers, Sean M Crosson, Manira Rayamajhi, Edward A Miao, Albert S Baldwin, Jennifer W Bradford
{"title":"Production of a p65<sup>fl/fl</sup>/LysMCre mouse model with dysfunctional NF-κB signaling in bone marrow-derived macrophages.","authors":"Ahmet K Korkaya, Jeffrey Fischer, Anthony Peppers, Sean M Crosson, Manira Rayamajhi, Edward A Miao, Albert S Baldwin, Jennifer W Bradford","doi":"10.1177/17534259231205993","DOIUrl":"10.1177/17534259231205993","url":null,"abstract":"<p><p>Here, we describe the production and characterization of a novel p65<sup>fl/fl</sup>/LysMCre mouse model, which lacks canonical nuclear factor-kappaB member RelA/p65 (indicated as p65 hereafter) in bone marrow-derived macrophages. Cultured bone marrow-derived macrophages that lack p65 protein reveal NF-κB signaling deficiencies, a reduction in phagocytic ability, and reduced ability to produce nitrites. Despite abnormal bone marrow-derived macrophage function, p65<sup>fl/fl</sup>/LysMCre mice do not exhibit differences in naïve systemic immune profiles or colony forming units and time to death following <i>Salmonella</i> infection as compared to controls. Additionally, p65<sup>fl/fl</sup>/LysMCre mice, especially females, display splenomegaly, but no other obvious physical or behavioral differences as compared to control animals. As bone marrow-derived macrophages from this transgenic model are almost completely devoid of canonical nuclear factor-kappaB pathway member p65, this model has the potential for being very useful in investigating bone marrow-derived macrophage NF-kappaB signaling in diverse biological and biomedical studies.</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":" ","pages":"171-185"},"PeriodicalIF":3.2,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10621469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41199833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Innate ImmunityPub Date : 2023-10-01Epub Date: 2023-08-22DOI: 10.1177/17534259231191252
Yusaku Tsugami, Takahiro Nii, Ken Kobayashi, Naoki Isobe
{"title":"Potential effects of gingerol topical application on components of the innate immunity in lactating goat mammary glands.","authors":"Yusaku Tsugami, Takahiro Nii, Ken Kobayashi, Naoki Isobe","doi":"10.1177/17534259231191252","DOIUrl":"10.1177/17534259231191252","url":null,"abstract":"<p><p>In the mammary glands, production of antimicrobial components and formation of less-permeable tight junctions (TJs) are important for safe milk production. Previously, we reported that local heat treatment of udders using disposable heating pad enhances the components of innate immunity in lactating goat mammary glands. Gingerol is a polyphenol present in ginger that can induce heat-like effects. However, oral administration of polyphenols causes a decrease in biological activity through conjugation and metabolic conversion. Here, we investigated the effects of gingerol on antimicrobial components and TJs by topically applying it to lactating goat udders. Gingerol application increased the somatic cell count, cathelicidin-2 concentration, and proportion of polymorphonuclear cells in the milk and interleukin-8 production. Moreover, gingerol treatment enhanced β-defensin-1 production in milk, cultured mammary epithelial cells, and cultured somatic cells. Contrastingly, gingerol treatment did not affect the concentrations of blood-derived components (Na<sup>+</sup>, albumin, and IgG) in the milk or the TJ barrier function of cultured mammary epithelial cells. These findings suggest that the topical application of gingerol, similar to local heat treatment, to udders enhances the components of innate immunity in mammary glands. These findings may be useful for the prevention of mastitis in milk-producing animals and, hence, safe and stable dairy production.</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":" ","pages":"135-149"},"PeriodicalIF":3.2,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/7e/68/10.1177_17534259231191252.PMC10559874.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10041380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Innate ImmunityPub Date : 2023-10-01DOI: 10.1177/17534259231186239
Young S Lee, I-Ting Cheng, Godoy-Ruiz Raquel, David J Weber, Joseph R Scalea
{"title":"Initial exploration of a novel fusion protein, IL-4/IL-34/IL-10, which promotes cardiac allograft survival mice through alloregulation.","authors":"Young S Lee, I-Ting Cheng, Godoy-Ruiz Raquel, David J Weber, Joseph R Scalea","doi":"10.1177/17534259231186239","DOIUrl":"10.1177/17534259231186239","url":null,"abstract":"<p><p>Immune mediated graft loss still represents a major risk to transplant recipients. Creative approaches to immunosuppression that exploit the recipient's own alloregulatory mechanisms could reduce the need for pharmacologic immunosuppression and potentially induce immune tolerance. In the process of studying recipient derived myeloid derived suppressor cells (MDSCs), we identified key alloregulatory MDSC mechanisms, mediated by isolatable proteins IL-4, IL-34, and IL-10. We sought to purify these proteins and fuse them for subsequent infusion into transplant recipients as a means of inducing an alloregulatory response. In this introductory investigation, we leveraged molecular engineering technology to create a fusion protein (FP) of three cytokine coding sequences of IL-4, IL-34, and IL-10 and demonstrated their expressions by Western Blot analysis. Following purification, we tested whether FP IL-4/IL-34/IL-10 (FP1) can protect heart transplant allografts. Injection of FP1 significantly prolonged allogeneic cardiac graft survival in a dose-dependent fashion and the increase of graft survival time exceeded survival attributable to IL-34 alone. In vitro, MDSCs cells were expanded by FP1 treatment. However, FP1 did not directly inhibit T cell proliferation in vitro. In conclusion, newly developed FP1 improves the graft survival in cardiac transplantation mouse model. Significant additional work to optimize FP1 or include other novel proteins could supplement current treatment options for transplant patients.</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"29 7","pages":"150-158"},"PeriodicalIF":2.8,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/bb/81/10.1177_17534259231186239.PMC10559875.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41134979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Innate ImmunityPub Date : 2023-08-01DOI: 10.1177/17534259231178223
Hamid Shegarfi
{"title":"Recognition of <i>Listeria monocytogenes</i> infection by natural killer cells: Towards a complete picture by experimental studies in rats.","authors":"Hamid Shegarfi","doi":"10.1177/17534259231178223","DOIUrl":"https://doi.org/10.1177/17534259231178223","url":null,"abstract":"<p><p>The study of cellular immune responses in animal disease models demands detailed knowledge of development, function, and regulation of immune cells, including natural killer (NK) cells. <i>Listeria monocytogenes</i> (<i>LM</i>) bacterium has been explored in a large area of research fields, including the host pathogen interaction. Although the importance role of NK cells in controlling the first phase of <i>LM</i> burden has been investigated, the interaction between NK cells and infected cells in details are far from being comprehended. From <i>in vivo</i> and <i>in vitro</i> experiments, we can drive several important pieces of knowledge that hopefully contribute to illuminating the intercommunication between <i>LM-</i>infected cells and NK cells. Experimental studies performed in rats revealed that certain NK cell ligands are influenced in <i>LM-</i>infected cells. These ligands include both classical- and non-classical MHC class I molecules and C-type lectin related (Clr) molecules that are ligands for Ly49- and NKR-P1 receptors respectively. Interaction between these receptors:ligands during <i>LM</i> infection, demonstrated stimulation of rat NK cells. Hence, these studies provided additional knowledge to the mechanisms NK cells utilise to recognise and respond to <i>LM</i> infection outlined in the current review.</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"29 6","pages":"110-121"},"PeriodicalIF":3.2,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c8/95/10.1177_17534259231178223.PMC10468624.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10489357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Innate ImmunityPub Date : 2023-08-01DOI: 10.1177/17534259231193926
Michael G Shehat, Madelyn H Miller, Ashley N Calder, Timothy A Gilbertson, Justine T Tigno-Aranjuez
{"title":"Dietary fat differentially modulates the response of bone marrow-derived macrophages to TLR4 and NOD2 agonists.","authors":"Michael G Shehat, Madelyn H Miller, Ashley N Calder, Timothy A Gilbertson, Justine T Tigno-Aranjuez","doi":"10.1177/17534259231193926","DOIUrl":"https://doi.org/10.1177/17534259231193926","url":null,"abstract":"<p><p>Consumption of diets high in fat has been linked to the development of obesity and related metabolic complications. Such associations originate from the enhanced, chronic, low-grade inflammation mediated by macrophages in response to translocated bacteria, bacterial products, or dietary constituents such as fatty acids (FAs). Nucleotide-binding Oligomerization Domain 2 (NOD2) senses muramyl dipeptide (MDP), a component of bacterial peptidoglycan. The inability to sense peptidoglycan through NOD2 has been demonstrated to lead to dysbiosis, increased bacterial translocation, inflammation and metabolic dysfunction. Currently, it is unknown how consumption of HFDs with different FA compositions might influence NOD2-dependent responses. In this study, we subjected WT mice to a control diet or to HFDs comprised of various ratios of unsaturated to saturated fats and determined the macrophage response to TLR4 and NOD2 agonists. A HFD with equal ratios of saturated and unsaturated fats enhanced subsequent responsiveness of macrophages to LPS but not to MDP. However, a high-unsaturated fat diet (HUFD) or a high-saturated fat diet (HSFD) both <i>decreased</i> the responsiveness to NOD2 agonists compared to that observed in control diet (CD) fed mice. These data suggest that dietary fatty acid composition can influence the subsequent macrophage responsiveness to bacterial products.</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"29 6","pages":"122-131"},"PeriodicalIF":3.2,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f9/55/10.1177_17534259231193926.PMC10468623.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10489899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Innate ImmunityPub Date : 2023-08-01DOI: 10.1177/17534259231189195
Xiaojing Zhang, Zhanfang Kang, Dazhong Yin, Jun Gao
{"title":"Role of neutrophils in different stages of atherosclerosis.","authors":"Xiaojing Zhang, Zhanfang Kang, Dazhong Yin, Jun Gao","doi":"10.1177/17534259231189195","DOIUrl":"https://doi.org/10.1177/17534259231189195","url":null,"abstract":"<p><p>Neutrophils constitute the first line of defense in human immunity and can be attracted to inflamed and infected sites by various chemokines. As essential players in immune processes, neutrophils theoretically play integral roles in the course of chronic inflammation-induced atherosclerosis. However, because neutrophils are rarely found in atherosclerotic lesions, their involvement in the pathophysiological progression of atherosclerosis has been largely underestimated or ignored. Recent research has revealed convincing evidence showing the presence of neutrophils in atherosclerotic lesions and has revealed neutrophil contributions to different atherosclerosis stages in mice and humans. This review describes the underlying mechanisms of neutrophils in different stages of atherosclerosis and highlights potential neutrophil-targeted therapeutic strategies relevant to atherosclerosis. An in-depth understanding of neutrophils' roles in atherosclerosis pathology will promote exploration of new methods for the prevention and treatment of atherogenesis and atherothrombosis.</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"29 6","pages":"97-109"},"PeriodicalIF":3.2,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1f/2f/10.1177_17534259231189195.PMC10468622.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10665759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Innate ImmunityPub Date : 2023-07-01Epub Date: 2023-06-12DOI: 10.1177/17534259231181029
Taylor Crue, Grace Yihua Lee, Joyce Yao-Chun Peng, Niccolette Schaunaman, Hina Agraval, Brian J Day, Kris Genelyn Dimasuay, Diana Cervantes, Hamid Nouri, Taylor Nichols, Paige Hartsoe, Mari Numata, Irina Petrache, Hong Wei Chu
{"title":"Single cell RNA-sequencing of human precision-cut lung slices: A novel approach to study the effect of vaping and viral infection on lung health.","authors":"Taylor Crue, Grace Yihua Lee, Joyce Yao-Chun Peng, Niccolette Schaunaman, Hina Agraval, Brian J Day, Kris Genelyn Dimasuay, Diana Cervantes, Hamid Nouri, Taylor Nichols, Paige Hartsoe, Mari Numata, Irina Petrache, Hong Wei Chu","doi":"10.1177/17534259231181029","DOIUrl":"10.1177/17534259231181029","url":null,"abstract":"<p><p>Vaping is an increasing health threat in the US and worldwide. The damaging impact of vaping on the human distal lung has been highlighted by the recent epidemic of electronic cigarette or vaping use-associated lung injury (EVALI). The pathogenesis of EVALI remains incompletely understood, due to a paucity of models that recapitulate the structural and functional complexity of the human distal lung and the still poorly defined culprit exposures to vaping products and respiratory viral infections. Our aim was to establish the feasibility of using single cell RNA-sequencing (scRNA-seq) technology in human precision-cut lung slices (PCLS) as a more physiologically relevant model to better understand how vaping regulates the antiviral and pro-inflammatory response to influenza A virus infection. Normal healthy donor PCLS were treated with vaping extract and influenza A viruses for scRNA-seq analysis. Vaping extract augmented host antiviral and pro-inflammatory responses in structural cells such as lung epithelial cells and fibroblasts, as well as in immune cells such as macrophages and monocytes. Our findings suggest that human distal lung slice model is useful to study the heterogeneous responses of immune and structural cells under EVALI conditions, such as vaping and respiratory viral infection.</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"29 5","pages":"61-70"},"PeriodicalIF":3.2,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/4e/df/10.1177_17534259231181029.PMC10357887.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9846417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Innate ImmunityPub Date : 2023-07-01DOI: 10.1177/17534259231178592
Daniela Maira Cardozo, Amanda Vansan Marangon, Fernando Guimarães, Silvia Marques, Sofia Lieber, Márcia Delamain, Francisco Aranha, Jeane Eliete Laguila Visentainer, Cármino Antonio de Souza
{"title":"Killer cell immunoglobulin-like receptor (KIR) genes and their HLA ligands in a Brazilian population.","authors":"Daniela Maira Cardozo, Amanda Vansan Marangon, Fernando Guimarães, Silvia Marques, Sofia Lieber, Márcia Delamain, Francisco Aranha, Jeane Eliete Laguila Visentainer, Cármino Antonio de Souza","doi":"10.1177/17534259231178592","DOIUrl":"https://doi.org/10.1177/17534259231178592","url":null,"abstract":"<p><p>Killer cell immunoglobulin-like receptors (KIR) exhibit extensive diversity, giving rise to different KIR profiles in populations worldwide. This study aimed to investigate the distribution of KIR genes and HLA ligands in a population from Campinas, southeastern Brazil (n = 292), and to compare their results with other populations. A comprehensive analysis of population-specific genes, genotype, and haplotype frequencies of KIR may facilitate a better understanding of their evolution and role in immunity. The genotyping of 16 KIR genes and HLA class I alleles was performed by the reverse sequence-specific oligonucleotide methodology using the Luminex platform (One Lambda, Inc., Canoga Park, CA). The framework genes were present in all individuals, with the most common non-framework KIR genes detected being KIR2DP1(96.6%), KIR2DL1(95.5%), KIR3DL1(94.5%), KIR2DS4(93.8%) and KIR2DL3(87.3%). KIR2DS1, KIR2DS3, KIR2DS5, and KIR3DS1 presented frequencies below 40%. KIR2DL2, KIR2DL5, and KIR2DS2 showed intermediate frequencies (between53% and 58%). The activating gene KIR2DS5 was the least common in this population (30.8%). Forty-five KIR profiles were found with the commonest being the homozygous A haplotype (27.4%). The distribution of KIR genes in the Brazilian population is similar to Caucasian European and Euro-descendant populations.</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"29 5","pages":"71-82"},"PeriodicalIF":3.2,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/82/6f/10.1177_17534259231178592.PMC10357888.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9903303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Innate ImmunityPub Date : 2023-07-01DOI: 10.1177/17534259231178594
Nada H Aljarba, Mashael R Al-Anazi, Tahani M Al-Hazani, Mohammed I Shafeai, Fuad H Rudiny, Ali M Motaen, Saad M Bin Dajem, Hani Alothaid, Jahad Alghamdi, Saad Alkahtani, Ahmed A Al-Qahtani
{"title":"Association between interleukin-27 gene polymorphisms and <i>Plasmodium falciparum</i> Malaria.","authors":"Nada H Aljarba, Mashael R Al-Anazi, Tahani M Al-Hazani, Mohammed I Shafeai, Fuad H Rudiny, Ali M Motaen, Saad M Bin Dajem, Hani Alothaid, Jahad Alghamdi, Saad Alkahtani, Ahmed A Al-Qahtani","doi":"10.1177/17534259231178594","DOIUrl":"https://doi.org/10.1177/17534259231178594","url":null,"abstract":"<p><p>Malaria is often characterized by a complicated disease course due to multifaceted intrinsic genetic factors of the host and the parasite. This study aimed to investigate the role of interleukin-27 (<i>IL-27</i>) gene polymorphisms in <i>Plasmodium falciparum</i> malaria infection in a Saudi Arabian cohort. This case-control study obtained blood samples from 250 malaria patients with <i>P. falciparum</i> and 200 randomly identified healthy control subjects from the Malaria Center in the Jazan area. Malaria patients were grouped into three cohorts as follow: low (<500 parasites/µl of blood), moderate (500-1000 parasites/µl of blood), and high (>1000 parasites/µl of blood) parasitemia. The results show that the IL-27 variant rs181209 was significantly associated with malaria patients (<i>P</i> = 0.026). Similarly, the homozygous GG genotype of rs26528 was also associated with risk of developing <i>P. falciparum</i> malaria (<i>P</i> = 0.032). The minor allele C of variant rs181206 exhibited an association with low to moderate parasitemia (<i>P</i> = 0.046). Furthermore, the rs181209 AA genotype was statistically significant in age group 1-5 years (<i>P</i> = 0.049). In conclusion, this study suggests that variant rs181209 and rs26528 could be associated with the risk of malaria infection by <i>P. falciparum</i> in the population studied.</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"29 5","pages":"83-94"},"PeriodicalIF":3.2,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c4/c3/10.1177_17534259231178594.PMC10357889.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9846415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Innate ImmunityPub Date : 2023-04-01DOI: 10.1177/17534259231168725
Jodi F Hedges, Deann T Snyder, Amanda Robison, Macy A Thompson, Klara Aspelin, Jack Plewa, Jory Baldridge, Mark A Jutila
{"title":"A TLR4 agonist liposome formulation effectively stimulates innate immunity and enhances protection from bacterial infection.","authors":"Jodi F Hedges, Deann T Snyder, Amanda Robison, Macy A Thompson, Klara Aspelin, Jack Plewa, Jory Baldridge, Mark A Jutila","doi":"10.1177/17534259231168725","DOIUrl":"https://doi.org/10.1177/17534259231168725","url":null,"abstract":"<p><p>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 <i>in vitro</i> using mammalian cells and <i>in vivo</i> in mice, and assessed indicators of innate immune responses and protection from bacterial infection. Lipo-CRX is similar to <i>E. coli</i> 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 <i>B. abortus</i>. While lipo-CRX or the antibiotic ampicillin alone did not alter <i>B. abortus</i> 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.</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"29 3-4","pages":"45-57"},"PeriodicalIF":3.2,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f7/20/10.1177_17534259231168725.PMC10331211.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9772012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}