Lymphocyte Immune Response Research Articles

The effects of CTL immune response on HIV infection model with potent therapy, latently infected cells and cell-to-cell viral transmission.

In this paper, a mathematical model is formulated to investigate the effect of cytotoxic T lymphocyte (CTL) immune response on human immunodeficiency virus (HIV) infection dynamics. The model includes latently infected cells, antiretroviral therapy, cell-free virus infection and cell-to- cell viral transmission. By constructing Lyapunov functionals, the global stability of three equilibria is obtained. More specifically, the infection-free equilibrium $E_{f}$ is globally asymptotically stable when the basic reproductive numbers $\mathcal{R}_{0}<1 implying="" that="" the="" virus="" can="" be="" eventually="" cleared="" the="" infected="" equilibrium="" without="" immune="" response="" e_="" w="" is="" globally="" asymptotically="" stable="" when="" the="" ctl="" immune="" response="" reproduction="" number="" mathcal="" r="" _="" 1="" is="" less="" than="" one="" and="" mathcal="" r="" _="" 0="" is="" greater="" than="" one="" implying="" that="" the="" infection="" becomes="" chronic="" but="" ctl="" immune="" response="" has="" not="" been="" established="" the="" infected="" equilibrium="" with="" immune="" response="" e_="" c="" is="" globally="" asymptotically="" stable="" when="" mathcal="" r="" _="" 1="">1$, implying that the infection becomes chronic with persistent CTL immune response. Numerical simulations confirm the above theoretical results. Moreover, the inclusion of CTL immune response can generate a higher level of uninfected CD4+ T cells, and significantly reduce infected cells and viral load. These results may help to improve the understanding of HIV infection dynamics.

Stability Analysis and Simulation of a Fractional-order HBV Infection Model Based on Saturation Incidence

Fractional order model has the memory, while the characteristic of the immune response contains the memory. In this paper, we set up a fractional-order HBV immune model based on saturation incidence for the first time. We derive the basic reproductive number R0, the cytotoxic T lymphocytes immune response reproductive number R1. There are three equilibrium points of our model, the local stability of each equilibrium point was given with corresponding hypothesis about R0 or R1. Finally we also give some numerical simulation, the simulation shows the individual difference in clinical may be reflected by fractional-order model.

Effects of polysaccharide-containing aqueous extracts of Cistanche deserticola Y. C. Ma on T lymphocyte subsets and duration of antibody response

Objective To study the effects of aqueous extracts of cultivated Cistanche deserticola Y. C. Ma (AECCD) on T cell responses and the duration of antibody response and to investigate its immunoenhancing activities in mice. Methods Two batches of female ICR mice were used in this study with 30 from each batch. Each batch of mice was randomly divided into six groups (n=5). Low, medium and high doses of AECCD in combination with ovalbumin (OVA) were used to set up three experimental groups, while 0.9% NaCl, OVA alone and aluminium adjuvant were respectively used as blank, negative and positive controls. All mice were intramuscularly injected twice at an interval of two weeks. Flow cytometry was used to detect the expression of T lymphocyte subsets, cytokines and surface molecules of dendritic cells (DC). Indirect ELISA was used to detect IgG antibody levels. Results AECCD could significantly increase the percentage of CD4+ and CD8+ T lymphocytes in spleen (P<0.05), up-regulate the expression of CD4+ CD44+ and CD8+ CD44+ effector T lymphocytes (P<0.05), promote the secretion of IFN-γ in T lymphocytes and enhance the expression of CD40 and CD80 on the surface of DC (P<0.05). ELISA results showed that high-dose AECCD could significantly prolong the duration of IgG antibody response induced by OVA (P<0.05). Conclusion AECCD could enhance the T lymphocyte immune response induced by OVA and keep it maintained at a high level, which might help to improve the body′s immune response. Key words: Cultivated Cistanche deserticola Y. C. Ma; T cell response; Immune enhancement

Characterization of CD40+ leukocytes in flounder (Paralichthys olivaceus) and its response after Hirame novirhabdovirus infection and immunization

CD40 is a crucial signal mediating factor in T-dependent B cell responses and involved in many aspects of cellular and humoral immunity. In this paper, recombinant protein of CD40 in flounder (Paralichthys olivaceus) and its antibodies (Abs) were produced, native CD40 molecules in flounder tissues were identified, then the CD40+ leukocytes in T/B lymphocytes were characterized, and the variations of CD40+ leukocytes in flounder after Hirame novirhabdovirus (HIRRV) infection and immunization were investigated, respectively. The results showed that the Abs could specifically recognize native flounder CD40 molecule at 32 kDa. The proportions of CD40+ leukocytes were varied by flounder tissues. CD40+/IgM+ B lymphocytes, CD40+/CD4-1+ T lymphocytes, CD40+/CD4-2+ T lymphocytes and CD40+/CD8+ T lymphocytes in peripheral blood leukocytes (PBLs) were 1.18 ± 0.27%, 0.69 ± 0.17%, 0.75 ± 0.14% and 0.25 ± 0.14%; were 2.80 ± 0.32%, 0.71 ± 0.19%, 0.88 ± 0.23% and 0.33 ± 0.17% in spleen; 4.11 ± 0.47%, 0.92 ± 0.18%, 1.09 ± 0.17% and 0.9 ± 0.17% in head kidney; 1.92 ± 0.39%, 1.02 ± 0.23%, 1.33 ± 0.38% and 0.67 ± 0.24% in intestine; 1.24 ± 0.36%, 1.21 ± 0.24%, 1.70 ± 0.3% and 0.97 ± 0.21% in gill, respectively. The percentages of CD40+ leukocytes in PBLs were significantly increased in both HIRRV infection and immunization groups, and reached their peak levels at 3rd day with 5.70 ± 0.16% and 6.40 ± 0.13%, respectively. Concluded with our previous study, these data first reported that CD40 molecules were expressed on both B and T lymphocytes in teleost, and had a coordination with T and B lymphocytes in immune responses.

Influence of CD4-1+, CD4-2+ and CD8+ T lymphocytes subpopulations on the immune response of B lymphocytes in flounder (Paralichthys olivaceus) immunized with thymus-dependent or thymus-independent antigen

In order to elucidate the influence of T lymphocytes subpopulations on B lymphocytes immune response, in this paper, CD4-1+, CD4-2+, CD8+ T lymphocytes and B lymphocytes responses to thymus-independent (TI) or thymus-dependent (TD) antigen plus immunosuppressant were investigated in flounder (Paralichthys olivaceus). The results showed that in LPS-immunized group, the percentages of CD4-1+, CD4-2+, CD8β+ T (PCD4-1+ T, PCD4-2+ T and PCD8β+ T) lymphocytes in peripheral blood leucocytes (PBLs) had no significant variations, the percentages of IgM+ B (PIgM+ B) lymphocytes and LPS-specific antibodies (LA) significantly increased and peaked at 3rd or 4th week post-injection; CsA had no inhibition on both T/B lymphocytes and LA; RaPa only suppressed the PIgM+ B lymphocytes and LA, and the inhibition maximum (Imax) were about 35% and 20%, respectively. In KLH-immunized group, the PCD4-1+, PCD4-2+ and PCD8β+ T lymphocytes significantly increased and peaked at 3rd or 5th day, successively the PIgM+ B lymphocytes and KLH-specific antibodies (KA) significantly increased to the peak at 5th week; the PCD4-1+, PCD4-2+ T and PIgM+ B lymphocytes and LA were inhibited significantly by both CsA and RaPa, and the Imax on them were 13%–33%, 11%–25%, 19%–34%, 22%–26%, respectively, while the PCD8β+ T lymphocytes showed no significant suppression. The results indicated that the suppression of PIgM+ B lymphocytes in KLH + CsA group was not directly derived from CsA, but due to the suppression of T lymphocytes, especially CD4+ T lymphocytes subpopulations. The results showed for the first time that, similar to higher vertebrates, T lymphocytes didn't respond to TI antigen, moreover, T lymphocyte subpopulations had a regulation on the immune response of B lymphocyte for TD antigen in flounder.

Analysis the Level of HPV16 E1 Specific Cytotoxic Lymphocyte Immune Response in Peripheral Blood of Advanced Cervical Cancer Patients with Clinical Features and Prognostic Factors

To measured the level of HPV16 E1 specific cytotoxic lymphocyte(CTL) immune response in peripheral blood of advanced cervical cancer patients. And to investigate the association of immune response with the clinical characteristics and prognosis of cervical cancer patients. To collected 77 cases with FIGO stage IIB-IIIB and pathological diagnosed cervical squamous cell carcinoma from March 2014 to October 2015 in our hospital. To examined the level of HPV16 E1 specific CTL response by using ELISpot assay and to confirmed the significance of prognostic factors. All patients were treated by radiation. (1)There was no significant difference in the frequency of HPV16 E1 specific CTL response with clinical characteristics of cervical cancer patients (P>0.05). There were statistically differences on intensity of HPV16 E1 specific CTL response between patients with stage II and III clinical staging group, HR-HPV-negative and positive group , TSGF normal and abnormal group and pelvic lymph node metastasis group (Z value and Pvalues were -2.273 and 0.023, -2.05 and 0.04, -2.05 and 0.04, -2.247 and 0.025 respectively ). (2)Univariate analysis showed that HR-HPV-negative and positive and HPV16 E1 specific CTL negative and positive response affected PFS, OS of cervical cancer patients (PFS:X2=4.94 and P=0.026, OS:X2=7.456 and P=0.006; PFS:X2=4.747 and P=0.029, OS: X2=3.97 and P=0.046) . Multivariate Cox regression analysis showed that HPV16 E1 specific CTL response was an important factor influencing PFS of cervical cancer patients (HR=0.372, 95% CI=0.134-1.028, P=0.038). HR-HPV affected PFS and OS of cervical cancer patients (PFS: HR=0.251, 95% CI=0.085-0.737, P=0.036; OS: HR=0.157, 95% CI=0.042-0.583, P=0.012). (3)The survival curves showed that the survival rate of OS and PFS in patients with HPV16 E1 specific CTL positive response was significantly higher than negative patients(OS: P=0.046; PFS: P=0.029). Patients with HR-HPV-negative had poorer OS and PFS than HR-HPV-positive, the difference was statistically significant (OS: P=0.015; PFS: P= 0.004). The level of HPV16 E1 specific CTL response and HR-HPV affect the survival of advanced cervical cancer patients, specifically the patients who had HR-HPV-negative or HPV16 E1 specific CTL negative response with poor prognosis.

Molecular architecture and regulation of BCL10-MALT1 filaments

The CARD11-BCL10-MALT1 (CBM) complex triggers the adaptive immune response in lymphocytes and lymphoma cells. CARD11/CARMA1 acts as a molecular seed inducing BCL10 filaments, but the integration of MALT1 and the assembly of a functional CBM complex has remained elusive. Using cryo-EM we solved the helical structure of the BCL10-MALT1 filament. The structural model of the filament core solved at 4.9 Å resolution identified the interface between the N-terminal MALT1 DD and the BCL10 caspase recruitment domain. The C-terminal MALT1 Ig and paracaspase domains protrude from this core to orchestrate binding of mediators and substrates at the filament periphery. Mutagenesis studies support the importance of the identified BCL10-MALT1 interface for CBM complex assembly, MALT1 protease activation and NF-κB signaling in Jurkat and primary CD4 T-cells. Collectively, we present a model for the assembly and architecture of the CBM signaling complex and how it functions as a signaling hub in T-lymphocytes.

Activation of PD-1 Protects Intestinal Immune Defense Through IL-10/miR-155 Pathway After Intestinal Ischemia Reperfusion.

To date, mechanisms of intestinal immunoglobulin (Ig) dysfunction following intestinal ischemia/reperfusion (I/R) remain unclear. Programmed death 1 (PD-1) is associated with immune responses of lymphocytes. We aimed to verify the hypothesis that activation of PD-1 may improve intestinal immune dysfunction by regulating IL-10/miR-155 production after intestinal IR injury. Intestinal I/R injury was induced in mice by clamping the superior mesenteric artery for 1h followed by 2-h reperfusion. PD-L1 fusion Ig, anti-interleukin (IL)-10 monoclonal antibody (mAb), and microRNA (miR)-155 agomir were administered. PD-1 expression, IL-10 mRNA, and protein expression in Peyer's patches (PP) CD4+ cells were measured. MiR-155 levels, tumor necrosis factor (TNF)-α and IL-1β concentration, and activation-induced cytidine deaminase (AID), a key enzyme for intestinal immune antibodies, in PP tissues were measured, respectively. Importantly, the production and cecal bacteria-binding capacity of IgA and IgM were detected. Intestinal I/R led to decreased PD-1 expression, imbalanced production, and impaired bacteria-binding capacity of IgA and IgM. Activating PD-1 by PD-L1 Ig facilitated IL-10 synthesis, then decreased miR-155 levels, and subsequently promoted AID expression and reduced TNF-α, IL-1β concentration. Upregulation of AID improved the disruptions of intestinal immune barrier caused by IgA and IgM dysfunction. Anti-IL-10 mAb and miR-155 agomir abolished the protective effects of PD-L1 Ig on the intestinal immune defense. Activation of PD-1 with PD-L1 Ig relieves intestinal immune defensive injury through IL-10/miR-155 pathway following intestinal I/R attack. PD-1, IL-10, and miR-155 may be potential targets for the damages of intestinal barrier and immunity.

Stability of latent pathogen infection model with adaptive immunity and delays.

In this paper we propose and analyze a pathogen dynamics model with antibody and Cytotoxic T Lymphocyte (CTL) immune responses. We incorporate latently infected cells and three distributed time delays into the model. We show that the solutions of the proposed model are nonnegative and ultimately bounded. We derive four threshold parameters which fully determine the existence and stability of the five steady states of the model. Using Lyapunov functionals, we established the global stability of the steady states of the model. The theoretical results are confirmed by numerical simulations.

Dynamics of a Delayed Diffusive HBV Infection Model with Capsids and CTL Immune Response

In this article, a delayed reaction-diffusion model of hepatitis B virus (HBV) infection with HBV DNA-containing capsids and cytotoxic T lymphocyte (CTL) immune response is presented and investigated by incorporating the spatial mobility of both capsids and virions. Also, the discrete time delays in the production of productively infected hepatocytes and matured capsids are taken into account in this model. First, the well-posedness of the concerned model is established in terms of existence, uniqueness, non-negativity and boundedness of solutions. The threshold conditions in terms of basic reproduction number $$R_{0}$$ and immune response reproduction number $$R_{CTL}$$ for global stability of the three spatially homogeneous steady states are established by constructing appropriate Lyapunov functions and by using linearization technique. We show that disease-free steady state, immune-free steady state and interior steady state with CTL immune response are globally asymptotically stable if $$R_{0}\le 1$$ , $$R_{CTL}\le 1<R_{0}$$ and $$R_{CTL}>1$$ , respectively. Finally, several numerical simulations are carried out in order to illustrate the theoretical results obtained.

Stability of an adaptive immunity pathogen dynamics model with latency and multiple delays

We incorporate three distributed time delays into the model of pathogen dynamics with antibody and Cytotoxic T Lymphocyte (CTL) immune responses. We consider both actively and latently infected cells. The pathogen‐target incidence rate, production/proliferation, and removal rates of the cells and pathogens are represented by general nonlinear functions. We show that the solutions of the proposed model are nonnegative and ultimately bounded. We derive four threshold parameters that fully determine the existence and stability of the five steady states of the model. Using Lyapunov functionals, we established the global stability of the steady states of the model. The theoretical results are confirmed by numerical simulations.

Loss of the von-Hippel Lindau gene in osteocytes alters B lymphocyte development and immune response

Abstract The von-Hippel Lindau protein (VHL) regulates hypoxia-inducible factor (HIF) degradation. Conditional-deletion of VHL in osteoblasts and in hematopoietic progenitors have demonstrated a role for VHL in these cell types, but how changes in bone homeostasis affects immune development are not fully understood. Osteoblasts (OBs) support B cell development. OBs mature into osteocytes (OCYs) and to test if OCYs also support B cell development, we generated OCY-specific (Dmp-Cre) conditional VHL knockout (cKO) mice. cKO mice display dysregulated bone growth, high bone density, smaller bone marrow (BM) cavity volume, and overall decrease in BM cellularity compared to controls. In line with this, the frequencies and numbers of B cell precursors (B220+ IgM−), immature B (B220+ IgMint) and recirculating B (B220+ IgMhigh) cells in the bone marrow are significantly decreased. These data suggest that the change in bone homeostasis adversely affects B cell development in a cell-extrinsic manner. Although the absolute numbers of B cells in the spleens of cKOs were normal, we hypothesized that loss of VHL in OCYs could permanently and adversely affect B cell functional response. To test this, VHL cKO mice were immunized with a T-independent antigen (NP-Ficoll). IgM and IgG3 antigen-specific titers to NP-Ficoll in VHL cKOs were similar to WT mice. Testing of B cell responses to T-dependent antigens (NP-OVA) is ongoing. Taken together, our data suggest that OCY-specific VHL deletion might be helpful to increase bone density, but at the expense of B cell numbers. Further investigation is required to understand the molecular mechanisms by which VHL in OCYs contribute to its putative role as a B cell niche cell.

Disabling of lymphocyte immune response by Ebola virus.

Disabling of lymphocyte immune response by Ebola virus.

The Effects of Dendritic Cell Hypersensitivity on Persistent Viral Infection.

Caspase-8 (CASP8) is known as an executioner of apoptosis, but more recent studies have shown that it participates in the regulation of necroptosis and innate immunity. In this study, we show that CASP8 negatively regulates retinoic acid-inducible gene I (RIG-I) signaling such that, in its absence, stimulation of the RIG-I pathway in dendritic cells (DCs) produced modestly enhanced activation of IFN regulatory factor 3 with correspondingly greater amounts of proinflammatory cytokines. In addition, mice lacking DC-specific CASP8 (dcCasp8-/- mice) develop age-dependent symptoms of autoimmune disease characterized by hyperactive DCs and T cells, spleen and liver immunopathology, and the appearance of Th1-polarized CD4+ T cells. Such mice infected with chronic lymphocytic choriomeningitis virus, an RNA virus detected by RIG-I, mounted an enhanced lymphocytic choriomeningitis virus-specific immune response as measured by increased proportions of Ag-specific CD4+ T cells and multicytokine-producing CD4+ and CD8+ T cells. These results show that CASP8 subtly modulates DC maturation, which controls the spontaneous appearance of autoimmune T cells while simultaneously attenuating the acquired immune system and its potential to control a persistent viral infection.

Dynamics analysis of an HTLV‐1 infection model with mitotic division of actively infected cells and delayed CTL immune response

In this paper, we propose an improved human T‐cell leukemia virus type 1 infection model with mitotic division of actively infected cells and delayed cytotoxic T lymphocyte immune response. By constructing suitable Lyapunov functional and using LaSalle invariance principle, we investigate the global stability of the infection‐free equilibrium of the system. Our results show that the time delay can change stability behavior of the infection equilibrium and lead to the existence of Hopf bifurcations. Finally, numerical simulations are conducted to illustrate the applications of the main results.

Abstract OT1-02-01: A phase II study of anti-PD-1 (MK-3475) therapy in patients with metastatic inflammatory breast cancer (MIBC) or non-IBC triple negative breast cancer (non-IBC TNBC) who have achieved clinical response or stable disease to prior chemotherapy

Abstract Primary Objective: To assess the efficacy of MK-3475 as a single agent in patients with MIBC and non-IBC TNBC. The primary endpoint is disease control rate at the end of 4 months after receiving the treatment. We will also investigate the association between biomarkers in the peripheral blood and tumor tissue, safety and efficacy. Background: The extensive invasion of lymphatic vessels by tumor emboli in patients with IBC suggests that the host immune surveillance system is suboptimal or that the tumor cells have decreased immunogenicity through immune editing to avoid detection by the host. In the immune-competent host, tumor cells must overcome both innate and adaptive immunologic defenses of the host. The PD-1 receptor-ligand interaction is a major pathway hijacked by tumors to suppress immune control. MK-3475 is a potent and highly selective humanized mAb designed to block the interaction between PD-1 and its ligands, PD-L1 and PD-L2. MK-3475 strongly enhances T lymphocyte immune responses in cultured blood cells from healthy human donors, cancer patients, and primates. Mouse anti-PD-1, as a monotherapy, demonstrated efficacy in several syngeneic mouse tumor models. To date, no specific targeted therapeutic options exist for the treatment of MIBC and TNBC. After patients achieving a clinical response to systemic therapy, the maintenance of disease control is not guaranteed. Further, our recent publication suggests that IBC has immune dysfunction. Chemotherapies can debulk the disease volume but cannot be used for maintenance due to their toxicities. Using an anti PD-1 monoclonal antibody is a promising approach for this patient population. Study Design and Treatment Plan: This is a single arm phase II study. Up to 35 patients with HER2 negative MIBC or metastatic TN-IBC (MTNBC) who have achieved clinical response or stable disease after receiving any prior systemic therapy for metastatic/recurrent disease, and meet all other criteria will be eligible. Patients will receive MK-3475 200 mg IV every 3 weeks for up to 2 years. Statistical Considerations: The trial will be conducted using Simon's optimal two-stage design and the rate of disease control will be estimated accordingly. It is assumed that the MK-3475 single agent will have a disease control rate of 30%. A disease control rate of 10% or lower will be considered treatment failure and the regimen will be rejected under this circumstance. Status of the study: Activation Date: June 2015. 13 patients have been enrolled. Enrollment continues. Sponsor: Merck Sharp &amp; Dohme Corp. State of Texas appropriation for rare and aggressive breast cancer research. Citation Format: Willey JS, Parker CA, Valero V, Lim B, Reuben JM, Krishnamurthy S, Gong Y, Scoggins ME, Dryden MJ, Liu DD, Woodward WA, Ueno NT. A phase II study of anti-PD-1 (MK-3475) therapy in patients with metastatic inflammatory breast cancer (MIBC) or non-IBC triple negative breast cancer (non-IBC TNBC) who have achieved clinical response or stable disease to prior chemotherapy [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr OT1-02-01.

Altered Anandamide Metabolism in Microgravity: the “RESLEM” experiment

Altered Anandamide Metabolism in Microgravity: the “RESLEM” experiment

Stability of CTL immunity pathogen dynamics model with capsids and distributed delay

In this paper, a pathogen dynamics model with capsids and saturated incidence has been proposed and analyzed. Cytotoxic T Lymphocyte (CTL) immune response and two distributed time delays have been incorporated into the model. The nonnegativity and boundedness of the solutions of the proposed model have been shown. Two threshold parameters which fully determine the existence and stability of the three steady states of the model have been computed. Using the method of Lyapunov function, the global stability of the steady states of the model has been established. The theoretical results have been confirmed by numerical simulations.

Tumor lymphocyte immune response to preoperative radiotherapy in locally advanced rectal cancer: The LYMPHOREC study

ABSTRACTIntroduction: Some studies have suggested that baseline tumor-infiltrating-lymphocytes (TILs), such as CD8+ and FoxP3+ T-cells, may be associated with a better prognosis in colorectal cancer. We sought to investigate modulation of the immune response by preoperative radiotherapy (preopRT) and its impact on survival in locally advanced rectal cancer (LARC).Materials & Methods: We analyzed data for 237 patients with LARC who received RT. Density of TILS (CD8+ and FoxP3+) in intraepithelial (iTILs) and stromal compartments (sTILs) were evaluated from surgery pathological specimens and biopsies performed at baseline. The primary endpoint was to assess the impact of infiltration of the tumor or tumor site after preopRT on progression-free survival (PFS) and overall survival (OS). Secondary endpoints were the impact of dose fractionation scheme on TILs.Results: In univariate analysis, several factors significantly correlated (p<0.05) with PFS and/or OS (T-stage, M-stage, the delay between RT and surgery). A high level of post-treatment FoxP3+ TIL density correlated significantly with a better PFS (p = 0.007). In multivariate analysis, a decrease in the CD8+/FoxP3+ iTILs ratio after preopRT correlated with better PFS and OS (p = 0.049 and p = 0.024, respectively). More particularly, patients with a delta CD8+/FoxP3+ <−3.8 had better PFS and OS. Interestingly, the dose fractionation scheme significantly influenced the CD8+/FoxP3+ ratio after treatment (p = 0.027) with a lower ratio with hypofractionated RT (≥2 Gy).Conclusion: Patients with LARC who had a significant decrease in the CD8+/FoxP3+ ratio after preopRT were more likely to live longer. This ratio needs to be validated prospectively to guide physicians in adjuvant treatment decision-making.

Epithelial-derived TGF-\u03b21 acts as a pro-viral factor in the lung during influenza A infection

Mucosal surfaces are under constant bombardment from potentially antigenic particles and so must maintain a balance between homeostasis and inappropriate immune activation and consequent pathology. Epithelial cells have a vital role orchestrating pulmonary homeostasis and defense against pathogens. TGF-β regulates an array of immune responses—both inflammatory and regulatory—however, its function is highly location- and context-dependent. We demonstrate that epithelial-derived TGF-β acts as a pro-viral factor suppressing early immune responses during influenza A infection. Mice specifically lacking bronchial epithelial TGF-β1 (epTGFβKO) displayed marked protection from influenza-induced weight loss, airway inflammation, and pathology. However, protection from influenza-induced pathology was not associated with a heightened lymphocytic immune response. In contrast, the kinetics of interferon beta (IFNβ) release into the airways was significantly enhanced in epTGFβKO mice compared with control mice, with elevated IFNβ on day 1 in epTGFβKO compared with control mice. This induced a heighted antiviral state resulting in impaired viral replication in epTGFβKO mice. Thus, epithelial-derived TGF-β acts to suppress early IFNβ responses leading to increased viral burden and pathology. This study demonstrates the importance of the local epithelial microenvironmental niche in shaping initial immune responses to viral infection and controlling host disease.