Immune NetworkPub Date : 2023-11-13eCollection Date: 2023-12-01DOI: 10.4110/in.2023.23.e43
Eliel Nham, Jineui Kim, Jungmin Lee, Heedo Park, Jeonghun Kim, Sohyun Lee, Jaeuk Choi, Kyung Taek Kim, Jin Gu Yoon, Soon Young Hwang, Joon Young Song, Hee Jin Cheong, Woo Joo Kim, Man-Seong Park, Ji Yun Noh
{"title":"Low Neutralizing Activities to the Omicron Subvariants BN.1 and XBB.1.5 of Sera From the Individuals Vaccinated With a BA.4/5-Containing Bivalent mRNA Vaccine.","authors":"Eliel Nham, Jineui Kim, Jungmin Lee, Heedo Park, Jeonghun Kim, Sohyun Lee, Jaeuk Choi, Kyung Taek Kim, Jin Gu Yoon, Soon Young Hwang, Joon Young Song, Hee Jin Cheong, Woo Joo Kim, Man-Seong Park, Ji Yun Noh","doi":"10.4110/in.2023.23.e43","DOIUrl":"10.4110/in.2023.23.e43","url":null,"abstract":"<p><p>The continuous emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants has provided insights for updating current coronavirus disease 2019 (COVID-19) vaccines. We examined the neutralizing activity of Abs induced by a BA.4/5-containing bivalent mRNA vaccine against Omicron subvariants BN.1 and XBB.1.5. We recruited 40 individuals who had received a monovalent COVID-19 booster dose after a primary series of COVID-19 vaccinations and will be vaccinated with a BA.4/5-containing bivalent vaccine. Sera were collected before vaccination, one month after, and three months after a bivalent booster. Neutralizing Ab (nAb) titers were measured against ancestral SARS-CoV-2 and Omicron subvariants BA.5, BN.1, and XBB.1.5. BA.4/5-containing bivalent vaccination significantly boosted nAb levels against both ancestral SARS-CoV-2 and Omicron subvariants. Participants with a history of SARS-CoV-2 infection had higher nAb titers against all examined strains than the infection-naïve group. NAb titers against BN.1 and XBB.1.5 were lower than those against the ancestral SARS-CoV-2 and BA.5 strains. These results suggest that COVID-19 vaccinations specifically targeting emerging Omicron subvariants, such as XBB.1.5, may be required to ensure better protection against SARS-CoV-2 infection, especially in high-risk groups.</p>","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"23 6","pages":"e43"},"PeriodicalIF":6.0,"publicationDate":"2023-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10767551/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139377498","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}
{"title":"NADPH Oxidase 4-mediated Alveolar Macrophage Recruitment to Lung Attenuates Neutrophilic Inflammation in <i>Staphylococcus aureus</i> Infection.","authors":"Seunghan Han, Sungmin Moon, Youn Wook Chung, Ji-Hwan Ryu","doi":"10.4110/in.2023.23.e42","DOIUrl":"https://doi.org/10.4110/in.2023.23.e42","url":null,"abstract":"<p><p>When the lungs are infected with bacteria, alveolar macrophages (AMs) are recruited to the site and play a crucial role in protecting the host by reducing excessive lung inflammation. However, the regulatory mechanisms that trigger the recruitment of AMs to lung alveoli during an infection are still not fully understood. In this study, we identified a critical role for NADPH oxidase 4 (NOX4) in the recruitment of AMs during <i>Staphylococcus aureus</i> lung infection. We found that NOX4 knockout (KO) mice showed decreased recruitment of AMs and increased lung neutrophils and injury in response to <i>S. aureus</i> infection compared to wild-type (WT) mice. Interestingly, the burden of <i>S. aureus</i> in the lungs was not different between NOX4 KO and WT mice. Furthermore, we observed that depletion of AMs in WT mice during <i>S. aureus</i> infection increased the number of neutrophils and lung injury to a similar level as that observed in NOX4 KO mice. Additionally, we found that expression of intercellular adhesion molecule-1 (ICAM1) in NOX4 KO mice-derived lung endothelial cells was lower than that in WT mice-derived endothelial cells. Therefore, we conclude that NOX4 plays a crucial role in inducing the recruitment of AMs by controlling ICAM1 expression in lung endothelial cells, which is responsible for resolving lung inflammation during acute <i>S. aureus</i> infection.</p>","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"23 5","pages":"e42"},"PeriodicalIF":6.0,"publicationDate":"2023-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10643333/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134650851","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}
Immune NetworkPub Date : 2023-10-23eCollection Date: 2023-10-01DOI: 10.4110/in.2023.23.e41
Paytsar Topchyan, Siying Lin, Weiguo Cui
{"title":"The Role of CD4 T Cell Help in CD8 T Cell Differentiation and Function During Chronic Infection and Cancer.","authors":"Paytsar Topchyan, Siying Lin, Weiguo Cui","doi":"10.4110/in.2023.23.e41","DOIUrl":"https://doi.org/10.4110/in.2023.23.e41","url":null,"abstract":"<p><p>CD4 and CD8 T cells are key players in the immune response against both pathogenic infections and cancer. CD4 T cells provide help to CD8 T cells via multiple mechanisms, including licensing dendritic cells (DCs), co-stimulation, and cytokine production. During acute infection and vaccination, CD4 T cell help is important for the development of CD8 T cell memory. However, during chronic viral infection and cancer, CD4 helper T cells are critical for the sustained effector CD8 T cell response, through a variety of mechanisms. In this review, we focus on T cell responses in conditions of chronic Ag stimulation, such as chronic viral infection and cancer. In particular, we address the significant role of CD4 T cell help in promoting effector CD8 T cell responses, emerging techniques that can be utilized to further our understanding of how these interactions may take place in the context of tertiary lymphoid structures, and how this key information can be harnessed for therapeutic utility against cancer.</p>","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"23 5","pages":"e41"},"PeriodicalIF":6.0,"publicationDate":"2023-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10643329/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134648853","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}
Immune NetworkPub Date : 2023-10-19eCollection Date: 2023-10-01DOI: 10.4110/in.2023.23.e40
Yonghae Son, Bo-Young Kim, Miran Kim, Jaesung Kim, Ryuk Jun Kwon, Koanhoi Kim
{"title":"Glucocorticoids Impair the 7α-Hydroxycholesterol-Enhanced Innate Immune Response.","authors":"Yonghae Son, Bo-Young Kim, Miran Kim, Jaesung Kim, Ryuk Jun Kwon, Koanhoi Kim","doi":"10.4110/in.2023.23.e40","DOIUrl":"https://doi.org/10.4110/in.2023.23.e40","url":null,"abstract":"<p><p>Glucocorticoids suppress the vascular inflammation that occurs under hypercholesterolemia, as demonstrated in an animal model fed a high-cholesterol diet. However, the molecular mechanisms underlying these beneficial effects remain poorly understood. Because cholesterol is oxidized to form cholesterol oxides (oxysterols) that are capable of inducing inflammation, we investigated whether glucocorticoids affect the immune responses evoked by 7α-hydroxycholesterol (7αOHChol). The treatment of human THP-1 monocytic cells with dexamethasone (Dex) and prednisolone (Pdn) downregulated the expression of pattern recognition receptors (PRRs), such as TLR6 and CD14, and diminished 7αOHChol-enhanced response to FSL-1, a TLR2/6 ligand, and lipopolysaccharide, which interacts with CD14 to initiate immune responses, as determined by the reduced secretion of IL-23 and CCL2, respectively. Glucocorticoids weakened the 7αOHChol-induced production of CCL2 and CCR5 ligands, which was accompanied by decreased migration of monocytic cells and CCR5-expressing Jurkat T cells. Treatment with Dex or Pdn also reduced the phosphorylation of the Akt-1 Src, ERK1/2, and p65 subunits. These results indicate that both Dex and Pdn impair the expression of PRRs and their downstream products, chemokine production, and phosphorylation of signaling molecules. Collectively, glucocorticoids suppress the innate immune response and activation of monocytic cells to an inflammatory phenotype enhanced or induced by 7αOHChol, which may contribute to the anti-inflammatory effects in hypercholesterolemic conditions.</p>","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"23 5","pages":"e40"},"PeriodicalIF":6.0,"publicationDate":"2023-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10643330/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134648852","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}
Immune NetworkPub Date : 2023-10-17eCollection Date: 2023-10-01DOI: 10.4110/in.2023.23.e39
Hyunjae Shin, Ha Seok Lee, Ji Yun Noh, June-Young Koh, So-Young Kim, Jeayeon Park, Sung Won Chung, Moon Haeng Hur, Min Kyung Park, Yun Bin Lee, Yoon Jun Kim, Jung-Hwan Yoon, Jae-Hoon Ko, Kyong Ran Peck, Joon Young Song, Eui-Cheol Shin, Jeong-Hoon Lee
{"title":"COVID-19 Vaccination Alters NK Cell Dynamics and Transiently Reduces HBsAg Titers Among Patients With Chronic Hepatitis B.","authors":"Hyunjae Shin, Ha Seok Lee, Ji Yun Noh, June-Young Koh, So-Young Kim, Jeayeon Park, Sung Won Chung, Moon Haeng Hur, Min Kyung Park, Yun Bin Lee, Yoon Jun Kim, Jung-Hwan Yoon, Jae-Hoon Ko, Kyong Ran Peck, Joon Young Song, Eui-Cheol Shin, Jeong-Hoon Lee","doi":"10.4110/in.2023.23.e39","DOIUrl":"https://doi.org/10.4110/in.2023.23.e39","url":null,"abstract":"<p><p>Coronavirus disease 2019 (COVID-19) vaccination may non-specifically alter the host immune system. This study aimed to evaluate the effect of COVID-19 vaccination on hepatitis B surface Ag (HBsAg) titer and host immunity in chronic hepatitis B (CHB) patients. Consecutive 2,797 CHB patients who had serial HBsAg measurements during antiviral treatment were included in this study. Changes in the HBsAg levels after COVID-19 vaccination were analyzed. The dynamics of NK cells following COVID-19 vaccination were also examined using serial blood samples collected prospectively from 25 healthy volunteers. Vaccinated CHB patients (n=2,329) had significantly lower HBsAg levels 1-30 days post-vaccination compared to baseline (median, -21.4 IU/ml from baseline), but the levels reverted to baseline by 91-180 days (median, -3.8 IU/ml). The velocity of the HBsAg decline was transiently accelerated within 30 days after vaccination (median velocity: -0.06, -0.39, and -0.04 log<sub>10</sub> IU/ml/year in pre-vaccination period, days 1-30, and days 31-90, respectively). In contrast, unvaccinated patients (n=468) had no change in HBsAg levels. Flow cytometric analysis showed that the frequency of NK cells expressing NKG2A, an NK inhibitory receptor, significantly decreased within 7 days after the first dose of COVID-19 vaccine (median, -13.1% from baseline; p<0.001). The decrease in the frequency of NKG2A<sup>+</sup> NK cells was observed in the CD56<sup>dim</sup>CD16<sup>+</sup> NK cell population regardless of type of COVID-19 vaccine. COVID-19 vaccination leads to a rapid, transient decline in HBsAg titer and a decrease in the frequency of NKG2A<sup>+</sup> NK cells.</p>","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"23 5","pages":"e39"},"PeriodicalIF":6.0,"publicationDate":"2023-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10643334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134648850","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}
Immune NetworkPub Date : 2023-09-22eCollection Date: 2023-10-01DOI: 10.4110/in.2023.23.e38
Sanjeeb Shrestha, Chang-Won Hong
{"title":"Extracellular Mechanisms of Neutrophils in Immune Cell Crosstalk.","authors":"Sanjeeb Shrestha, Chang-Won Hong","doi":"10.4110/in.2023.23.e38","DOIUrl":"10.4110/in.2023.23.e38","url":null,"abstract":"<p><p>Neutrophils are professional phagocytes that provide defense against invading pathogens through phagocytosis, degranulation, generation of ROS, and the formation of neutrophil extracellular traps (NETs). Although long been considered as short-lived effector cells with limited biosynthetic activity, recent studies have revealed that neutrophils actively communicate with other immune cells. Neutrophils employ various types of soluble mediators, including granules, cytokines, and chemokines, for crosstalk with immune cells. Additionally, ROS and NETs, major arsenals of neutrophils, are utilized for intercellular communication. Furthermore, extracellular vesicles play a crucial role as mediators of neutrophil crosstalk. In this review, we highlight the extracellular mechanisms of neutrophils and their roles in crosstalk with other cells.</p>","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"23 5","pages":"e38"},"PeriodicalIF":6.0,"publicationDate":"2023-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10643328/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134648851","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}
Immune NetworkPub Date : 2023-09-22eCollection Date: 2023-10-01DOI: 10.4110/in.2023.23.e37
Young-Saeng Jang, Sun-Hee Park, Seung-Goo Kang, Jung-Shin Lee, Hyun-Jeong Ko, Pyeung-Hyeun Kim
{"title":"Combined Treatment With TGF-β1, Retinoic Acid, and Lactoferrin Robustly Generate Inducible Tregs (iTregs) Against High Affinity Ligand.","authors":"Young-Saeng Jang, Sun-Hee Park, Seung-Goo Kang, Jung-Shin Lee, Hyun-Jeong Ko, Pyeung-Hyeun Kim","doi":"10.4110/in.2023.23.e37","DOIUrl":"https://doi.org/10.4110/in.2023.23.e37","url":null,"abstract":"<p><p>Forkhead box P3-positive (Foxp3<sup>+</sup>)-inducible Tregs (iTregs) are readily generated by TGF-β1 at low TCR signaling intensity. TGF-β1-mediated Foxp3 expression is further enhanced by retinoic acid (RA) and lactoferrin (LF). However, the intensity of TCR signaling required for induction of Foxp3 expression by TGF-β1 in combination with RA and LF is unknown. Here, we found that either RA or LF alone decreased TGF-β1-mediated Foxp3 expression at low TCR signaling intensity. In contrast, at high TCR signaling intensity, the addition of either RA or LF strongly increased TGF-β1-mediated Foxp3 expression. Moreover, decreased CD28 stimulation was more favorable for TGF-β1/LF-mediated Foxp3 expression. Lastly, we found that at high signaling intensities of both TCR and CD28, combined treatment with TGF-β1, RA, and LF induced robust expression of Foxp3, in parallel with powerful suppressive activity against responder T cell proliferation. Our findings that TGFβ/RA/LF strongly generate high affinity Ag-specific iTreg population would be useful for the control of unwanted hypersensitive immune reactions such as various autoimmune diseases.</p>","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"23 5","pages":"e37"},"PeriodicalIF":6.0,"publicationDate":"2023-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10643331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134648812","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}
Immune NetworkPub Date : 2023-08-21eCollection Date: 2023-10-01DOI: 10.4110/in.2023.23.e36
Sangsin Lee, Seung Geun Song, Doo Hyun Chung
{"title":"Comprehensive Transcriptomic Analysis for Thymic Epithelial Cells of Aged Mice and Humans.","authors":"Sangsin Lee, Seung Geun Song, Doo Hyun Chung","doi":"10.4110/in.2023.23.e36","DOIUrl":"https://doi.org/10.4110/in.2023.23.e36","url":null,"abstract":"<p><p>Thymic epithelial cells (TECs) play a critical role in thymic development and thymopoiesis. As individuals age, TECs undergo various changes that impact their functions, leading to a reduction in cell numbers and impaired thymic selection. These age-related alterations have been observed in both mice and humans. However, the precise mechanisms underlying age-related TEC dysfunction remain unclear. Furthermore, there is a lack of a comprehensive study that connects mouse and human biological processes in this area. To address this gap, we conducted an extensive transcriptome analysis of young and old TECs in mice, complemented by further analysis of publicly available human TEC single-cell RNA sequencing data. Our analysis revealed alterations in both known and unknown pathways that potentially contribute to age-related TEC dysfunction. Specifically, we observed downregulation of pathways related to cell proliferation, T cell development, metabolism, and cytokine signaling in old age TECs. Conversely, TGF-β, BMP, and Wnt signaling pathways were upregulated, which have been known to be associated with age-related TEC dysfunctions or newly discovered in this study. Importantly, we found that these age-related changes in mouse TECs were consistently present in human TECs as well. This cross-species validation further strengthens the significance of our findings. In conclusion, our comprehensive analysis provides valuable insight into the biological and immunological characteristics of aged TECs in both mice and humans. These findings contribute to a better understanding of thymic involution and age-induced immune dysfunction.</p>","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"23 5","pages":"e36"},"PeriodicalIF":6.0,"publicationDate":"2023-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10643332/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134648813","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}
Immune NetworkPub Date : 2023-08-04eCollection Date: 2023-08-01DOI: 10.4110/in.2023.23.e32
Hyun-Jung Kong, Youngwon Choi, Eun-Ah Kim, Jun Chang
{"title":"Vaccine Strategy That Enhances the Protective Efficacy of Systemic Immunization by Establishing Lung-Resident Memory CD8 T Cells Against Influenza Infection.","authors":"Hyun-Jung Kong, Youngwon Choi, Eun-Ah Kim, Jun Chang","doi":"10.4110/in.2023.23.e32","DOIUrl":"10.4110/in.2023.23.e32","url":null,"abstract":"<p><p>Most influenza vaccines currently in use target the highly variable hemagglutinin protein to induce neutralizing antibodies and therefore require yearly reformulation. T cell-based universal influenza vaccines focus on eliciting broadly cross-reactive T-cell responses, especially the tissue-resident memory T cell (T<sub>RM</sub>) population in the respiratory tract, providing superior protection to circulating memory T cells. This study demonstrated that intramuscular (i.m.) administration of the adenovirus-based vaccine expressing influenza virus nucleoprotein (rAd/NP) elicited weak CD8 T<sub>RM</sub> responses in the lungs and airways, and yielded poor protection against lethal influenza virus challenge. However, a novel \"prime-and-deploy\" strategy that combines i.m. vaccination of rAd/NP with subsequent intranasal administration of an empty adenovector induced strong NP-specific CD8<sup>+</sup> T<sub>RM</sub> cells and provided complete protection against influenza virus challenge. Overall, our results demonstrate that this \"prime-and-deploy\" vaccination strategy is potentially applicable to the development of universal influenza vaccines.</p>","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"23 4","pages":"e32"},"PeriodicalIF":4.3,"publicationDate":"2023-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ef/d9/in-23-e32.PMC10475829.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10160205","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}
Immune NetworkPub Date : 2023-08-03eCollection Date: 2023-08-01DOI: 10.4110/in.2023.23.e31
Gwanghee Kim, Yoojin Lee, Jin Sun You, Wontae Hwang, Jeewon Hwang, Hwa Young Kim, Jieun Kim, Ara Jo, In Ho Park, Mohammed Ali, Jongsun Kim, Jeon-Soo Shin, Ho-Keun Kwon, Hyun Jik Kim, Sang Sun Yoon
{"title":"A Moonlighting Protein Secreted by a Nasal Microbiome Fortifies the Innate Host Defense Against Bacterial and Viral Infections.","authors":"Gwanghee Kim, Yoojin Lee, Jin Sun You, Wontae Hwang, Jeewon Hwang, Hwa Young Kim, Jieun Kim, Ara Jo, In Ho Park, Mohammed Ali, Jongsun Kim, Jeon-Soo Shin, Ho-Keun Kwon, Hyun Jik Kim, Sang Sun Yoon","doi":"10.4110/in.2023.23.e31","DOIUrl":"10.4110/in.2023.23.e31","url":null,"abstract":"<p><p>Evidence suggests that the human respiratory tract, as with the gastrointestinal tract, has evolved to its current state in association with commensal microbes. However, little is known about how the airway microbiome affects the development of airway immune system. Here, we uncover a previously unidentified mode of interaction between host airway immunity and a unique strain (AIT01) of <i>Staphylococcus epidermidis</i>, a predominant species of the nasal microbiome. Intranasal administration of AIT01 increased the population of neutrophils and monocytes in mouse lungs. The recruitment of these immune cells resulted in the protection of the murine host against infection by <i>Pseudomonas aeruginosa</i>, a pathogenic bacterium. Interestingly, an AIT01-secreted protein identified as GAPDH, a well-known bacterial moonlighting protein, mediated this protective effect. Intranasal delivery of the purified GAPDH conferred significant resistance against other Gram-negative pathogens (<i>Klebsiella pneumoniae</i> and <i>Acinetobacter baumannii</i>) and influenza A virus. Our findings demonstrate the potential of a native nasal microbe and its secretory protein to enhance innate immune defense against airway infections. These results offer a promising preventive measure, particularly relevant in the context of global pandemics.</p>","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"23 4","pages":"e31"},"PeriodicalIF":4.3,"publicationDate":"2023-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/34/09/in-23-e31.PMC10475824.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10160206","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}