Innate and mild Th17 cutaneous immune responses elicited by subcutaneous infection of immunocompetent mice with Cladosporium cladosporioides

2021 ◽  
pp. 105384
Author(s):  
Xiaoping Ma ◽  
Jing Hu ◽  
Chengdong Wang ◽  
Yu Gu ◽  
Sanjie Cao ◽  
...  
Keyword(s):  
Immune Responses ◽  
Cladosporium Cladosporioides ◽  
Subcutaneous Infection ◽  
Immunocompetent Mice

scholarly journals Assessment of the pulmonary adaptive immune response to Cladosporium cladosporioides infection using an experimental mouse model

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xiaoping Ma ◽  
Jing Hu ◽  
Yan Yu ◽  
Chengdong Wang ◽  
Yu Gu ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Adaptive Immune Response ◽  
Pulmonary Hemorrhage ◽  
Cladosporium Cladosporioides ◽  
Th2 Cells ◽  
Intercellular Adhesion Molecule ◽  
Post Inoculation ◽  
Adaptive Immune ◽  
Systemic Infections

AbstractCladosporium cladosporioides causes asthma and superficial and deep infections, mostly in immunodeficient individuals and animals. This study aimed to investigate whether C. cladosporioides spores can enter the lungs through pulmonary circulation and influence pulmonary immune response. We intravenously injected mice with C. cladosporioides spore suspension and conducted several assays on the lungs. Pulmonary hemorrhage symptoms and congestion were most severe on days 1, 2, and 3 post-inoculation (PI). Extensive inflammatory cell infiltration occurred throughout the period of infection. More spores and hyphae colonizing the lungs were detected on days 1, 2, and 3 PI, and fewer spores and hyphae were observed within 21 d of infection. Numerous macrophages, dendritic cells, and neutrophils were observed on day 5 PI, along with upregulation of CD54, an intercellular adhesion molecule. Th1 and Th2 cells increased after infection; specifically, Th2 cells increased considerably on day 5 PI. These results suggest that days 2 and 5 PI represent the inflammatory peak in the lungs and that the Th2 and Th1 signaling pathways are potentially involved in pulmonary immune responses. In conclusion, the further adaptive immune responses played important roles in establishing effective pulmonary immunity against C. cladosporioides systemic infections based on innate immune responses.

scholarly journals ­ Apatinib combined with PD-L1 blockade synergistically enhances antitumor immune responses and promotes HEV formation in gastric cancer

2021 ◽  
Author(s):  
Yu Zhang ◽  
Fei Wang ◽  
Hao-ran Sun ◽  
Ya-kai Huang ◽  
Jian-peng Gao ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
T Cells ◽  
B Cells ◽  
Combination Therapy ◽  
Immune Responses ◽  
Cytotoxic T Cells ◽  
Antibody Therapy ◽  
Treg Cells ◽  
Cytotoxic T Cell ◽  
Immunocompetent Mice

Abstract Purpose Apatinib, an antiangiogenic drug, has showed beneficial effects only in a fraction of advanced gastric cancer (GC) patients. Given the recent success of immunotherapies, combination of apatinib with immune checkpoint inhibitor may provide sustained and potent antitumor responses. Methods Immunocompetent mice with subcutaneous MFC tumors grown were given combination of apatinib and anti-PD-L1 antibody therapy. GC tissues from patients undergoing curative resection in China were collected, and the density of HEVs, MSI status and tumor-infiltrated lymphocytes were analyzed by immunohistochemical staining. Results Combined apatinib and PD-L1 blockade therapy synergistically delayed tumor growth and increased survival in MFC-bearing immunocompetent mice. The combination therapy promoted antitumor immunity by increasing the ratio of CD8+ cytotoxic T cells to Foxp3+ Treg cells, the accumulation of CD20+ B cells and the Th1/Th2 cytokine ratio (IFN-γ/IL-10). The combination therapy induced the formation of HEVs through activation of LTβR signaling, thus promoting CD8+ cytotoxic T cell and CD20+ B cell infiltration in tumors. In clinical GC samples, the density of HEVs positively correlated with the intratumoral infiltration of CD8+ cytotoxic T cells and CD20+ B cells. MSI-high GC showed a higher density of HEVs, CD8+ cytotoxic T cells and CD20+ B cells than MSS/MSI-low GC. GC patients with high densities of HEVs, CD8+ cytotoxic T cells and CD20+ B cells had an improved prognosis with superior overall survival. Conclusion Combining apatinib with PD-L1 blockade treatment synergistically enhances antitumor immune responses and promotes HEV formation in GC.

scholarly journals Interferon α/β and Interleukin 12 Responses to Viral Infections

2002 ◽  
Vol 195 (4) ◽  
pp. 517-528 ◽  
Author(s):  
Marc Dalod ◽  
Thais P. Salazar-Mather ◽  
Lene Malmgaard ◽  
Casey Lewis ◽  
Carine Asselin-Paturel ◽  
...  
Keyword(s):  
Immune Responses ◽  
Viral Infections ◽  
Lymphocytic Choriomeningitis ◽  
Murine Cytomegalovirus ◽  
Interleukin 12 ◽  
Interferon Α ◽  
Type I ◽  
Type I Ifns ◽  
Immunocompetent Mice

Interferon (IFN)-α/β and interleukin (IL)-12 are cytokines critical in defense against viruses, but their cellular sources and mechanisms of regulation for in vivo expression remain poorly characterized. The studies presented here identified a novel subset of dendritic cells (DCs) as major producers of the cytokines during murine cytomegalovirus (MCMV) but not lymphocytic choriomeningitis virus (LCMV) infections. These DCs differed from those activated by Toxoplasma antigen but were related to plasmacytoid cells, as assessed by their CD8α+Ly6G/C+CD11b− phenotype. Another DC subset (CD8α2Ly6G/C−CD11b+) also contributed to IL-12 production in MCMV-infected immunocompetent mice, modestly. However, it dramatically increased IL-12 expression in the absence of IFN-α/β functions. Conversely, IFN-α/β production was greatly reduced under these conditions. Thus, a cross-regulation of DC subset cytokine responses was defined, whereby secretion of type I IFNs by CD8α+ DCs resulted in responses limiting IL-12 expression by CD11b+ DCs but enhancing overall IFN-α/β production. Taken together, these data indicate that CD8α+Ly6G/C+CD11b− DCs play important roles in limiting viral replication and regulating immune responses, through cytokine production, in some but not all viral infections. They also illustrate the plasticity of cellular sources for innate cytokines in vivo and provide new insights into the roles of IFNs in shaping immune responses to viruses.

scholarly journals Virus-Encoded B7-2 Costimulation Molecules Enhance the Protective Capacity of a Replication-Defective Herpes Simplex Virus Type 2 Vaccine in Immunocompetent Mice

2008 ◽  
Vol 83 (2) ◽  
pp. 953-960 ◽  
Author(s):  
Sri P. Vagvala ◽  
Lydia G. Thebeau ◽  
Saydra R. Wilson ◽  
Lynda A. Morrison
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Immune Responses ◽  
Progeny Virus ◽  
Vaginal Mucosa ◽  
Protective Capacity ◽  
Challenge Virus ◽  
Immunocompetent Mice ◽  
Simplex Virus ◽  
Defective Virus

ABSTRACT Herpes simplex virus 2 (HSV-2) and, to a lesser extent, HSV-1 cause the majority of sexually transmitted genital ulcerative disease. No effective prophylactic vaccine is currently available. Replication-defective HSV stimulates immune responses in animals but produces no progeny virus, making it potentially useful as a safe form of live vaccine against HSV. Because it does not replicate and spread in the host, however, replication-defective virus may have relatively limited capacity to solicit professional antigen presentation. We previously demonstrated that in mice devoid of B7-1 and B7-2 costimulation molecules, replication-defective HSV-2 encoding B7-1 or B7-2 induces stronger immune responses and protection against HSV-2 challenge than immunization with replication-defective virus alone. Here, we vaccinated wild-type mice fully competent to express endogenous B7 costimulation molecules with replication-defective HSV-2 or replication-defective virus encoding B7-2 and compared their capacities to protect against vaginal HSV-2 infection and disease. Replication-defective virus encoding B7-2 induced more IFN-γ-producing CD4 T cells than did replication-defective virus alone. Immunization with B7-2-expressing virus decreased challenge virus replication in the vaginal mucosa, genital and neurological disease, and mortality more effectively than did immunization with the parental replication-defective virus. Prior immunization with B7-expressing, replication-defective virus also effectively suppressed infection of the nervous system compared to immunization with the parental virus. Thus, B7 costimulation molecules expressed at the site of HSV infection can enhance vaccine efficacy even in a fully immunocompetent host.

scholarly journals Urokinase-Deficient Mice Fail To Generate a Type 2 Immune Response following Schistosomal Antigen Challenge

2004 ◽  
Vol 72 (1) ◽  
pp. 461-467 ◽  
Author(s):  
Margaret R. Gyetko ◽  
Sudha Sud ◽  
Stephen W. Chensue
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Immunoglobulin E ◽  
Interleukin 4 ◽  
Delayed Type Hypersensitivity ◽  
Alternative Response ◽  
Type Plasminogen Activator ◽  
Immune Defect ◽  
T1 And T2 ◽  
Immunocompetent Mice

ABSTRACT Activated lymphocytes express urokinase-type plasminogen activator (uPA). Previous work suggests that uPA modulates T-lymphocyte responses. Mice deficient in uPA (uPA−/−) fail to generate type 1 (T1) immune responses during infection with Cryptococcus neoformans. Failure to generate either a T1 or a T2 immune response is not predictive of defects in the alternative response. Conversely, down-regulation of one type of immune response may result in inappropriate overactivation of the other. It is not known whether the immune defect in uPA−/− mice affects only T1 responses or whether T2 responses are also impaired. Impairment of both T1 and T2 responses would suggest a global T-cell defect in the absence of uPA. To determine the role of uPA in T2 immune responses, wild-type (WT) and uPA−/− mice were primed and challenged with schistosomal egg antigen (SEA). This elicits strong polarization to T2 immune responses in immunocompetent mice. The challenged WT mice developed delayed-type hypersensitivity (DTH) to SEA; high levels of serum immunoglobulin E (IgE); a strong T2 cytokine phenotype with markedly elevated levels of interleukin-4 (IL-4), IL-5, and IL-13; and eosinophil-rich pulmonary granulomas. uPA−/− mice failed to develop DTH to SEA; did not polarize Ig production to IgE; did not produce high levels of IL-4, IL-5, or IL-13; and had markedly reduced numbers of granuloma-associated eosinophils. uPA−/− mice fail to generate polarized T2 immune responses to a T2-inducing pathogen. These findings, in conjunction with our previous work, demonstrate that mice deficient in uPA have profoundly impaired immunity involving both T1 and T2 polarization and are largely immunologically unresponsive.

scholarly journals Autophagy induction by thiostrepton improves the efficacy of immunogenic chemotherapy

2020 ◽  
Vol 8 (1) ◽  
pp. e000462 ◽  
Author(s):  
Yan Wang ◽  
Wei Xie ◽  
Juliette Humeau ◽  
Guo Chen ◽  
Peng Liu ◽  
...  
Keyword(s):  
Immune Responses ◽  
Atp Release ◽  
High Mobility ◽  
Fluorescent Biosensors ◽  
Adaptive Immune ◽  
Autophagy Induction ◽  
Screen Approach ◽  
Immunocompetent Mice ◽  
Do So

BackgroundImmunogenic cell death (ICD) is a peculiar modality of cellular demise that elicits adaptive immune responses and triggers T cell-dependent immunity.MethodsFluorescent biosensors were employed for an unbiased drug screen approach aiming at the identification of ICD enhancers.ResultsHere, we discovered thiostrepton as an enhancer of ICD able to boost chemotherapy-induced ATP release, calreticulin exposure and high-mobility group box 1 exodus. Moreover, thiostrepton enhanced anticancer immune responses of oxaliplatin (OXA) in vivo in immunocompetent mice, yet failed to do so in immunodeficient animals. Consistently, thiostrepton combined with OXA altered the ratio of cytotoxic T lymphocytes to regulatory T cells, thus overcoming immunosuppression and reinstating anticancer immunosurveillance.ConclusionAltogether, these results indicate that thiostrepton can be advantageously combined with chemotherapy to enhance anticancer immunogenicity.

scholarly journals Subretinal delivery of adeno-associated virus serotype 2 results in minimal immune responses that allow repeat vector administration in immunocompetent mice

2009 ◽  
Vol 11 (6) ◽  
pp. 486-497 ◽  
Author(s):  
Susie E. Barker ◽  
Cathryn A. Broderick ◽  
Scott J. Robbie ◽  
Yanai Duran ◽  
Mythili Natkunarajah ◽  
...  
Keyword(s):  
Immune Responses ◽  
Adeno Associated Virus ◽  
Virus Serotype ◽  
Immunocompetent Mice

scholarly journals Murine Norovirus Infection Has No Significant Effect on Adaptive Immunity to Vaccinia Virus or Influenza A Virus

2009 ◽  
Vol 83 (14) ◽  
pp. 7357-7360 ◽  
Author(s):  
Scott E. Hensley ◽  
Amelia K. Pinto ◽  
Heather D. Hickman ◽  
Robin J. Kastenmayer ◽  
Jack R. Bennink ◽  
...  
Keyword(s):  
Immune Responses ◽  
Vaccinia Virus ◽  
Adaptive Immunity ◽  
Influenza A Virus ◽  
Influenza A ◽  
Viral Infections ◽  
Host Immunity ◽  
Antibody Responses ◽  
Murine Norovirus ◽  
Immunocompetent Mice

ABSTRACT Murine norovirus (MNV) is endemic in many research mouse colonies. Although MNV infections are typically asymptomatic in immunocompetent mice, the effects of MNV infection on subsequent experimental viral infections are poorly documented. Here, we infected C57BL/6 mice with MNV and then with either vaccinia virus or influenza A virus. MNV infection had no effect on CD8+ T-cell or antibody responses to secondary viruses or to secondary virus-induced morbidity or mortality. While our findings suggest that MNV has little influence on host immunity in immunocompetent mice, we would urge caution regarding the potential effects of MNV on immune responses to viruses and other pathogens, which must be determined on a system-by-system basis.

scholarly journals Innate and Adaptive Immune Responses Induced by A. Fumigatus Conidia and Hyphae

2021 ◽  
Author(s):  
Yingzhi Luo ◽  
Fang Liu ◽  
Jie Xu ◽  
Qingtao Kong ◽  
Yi Shi ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Immune Responses ◽  
Protective Role ◽  
Rna Seq ◽  
Th1 Cell ◽  
Th2 Cell ◽  
Th17 Cell Differentiation ◽  
M1 Polarization ◽  
Immunocompetent Mice

Abstract Purpose Previous research indicated hyphae of A. fumigatus rather than conidia could successfully build pulmonary aspergillosis model in immunocompetent mice. In this study, we compared the immune responses induced by hyphae and conidia, making a preliminary explanation for the phenomenon.Methods Macrophages and PBMCs were respectively stimulated by A. fumigatus hyphae and conidia and immunological changes were measured in vitro. Male C57BL/6 mice were challenged with conidia and hyphae through intratracheal inoculation. Dynamic conditions of mice were recorded and their immune responses were measured by RNA-seq.Results The results confirmed that hyphae could induce more intensive inflammation than conidia. However, macrophages revealed a higher production of ROS as well as M1 polarization in response to conidia stimuli. In addition, conidia could promote Th1 cell differentiation, while hyphae could increase the CD4/CD8 ratio. RNA-seq validated that multiple immunologically relevant pathways were much more strongly activated by hyphae, which also promoted Th2 cell differentiation and suppressed Th1 cell differentiation. Both hyphae and conidia could activate Th17 cell differentiation.Conclusion Conidia and hyphae induced different immune responses and the immune responses against conidia played a better protective role.

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