Effect ofNocardia rubra cell-wall skeleton on cancer prevention in humans

Summary The retired workers at the chemical weapons plant in Japan are regarded as a high-risk group for cancers. Under the Cancer Preventive Program,Nocardia rubra cell-wall skeleton (N-CWS) was administered to 80 workers directly involved in the production of sulfur mustard and 66 workers engaged in work related to sulfur mustard production. Untreated workers whose age, sex, duties and duration of work at this factory were individually matched to the N-CWS-treated workers were used as controls. During a 4.5-year observation period, development of cancers was found in 7 treated workers and 17 untreated controls. After elimination of the influence of the difference in smoking level, the incidence of subjects who developed cancers was compared statistically between the N-CWS-treated workers and the untreated controls and a significant suppression of development of cancers was noted in the N-CWS-treated workers. Thus, it was concluded that the administration of N-CWS could prevent cancer development in humans.     

Clinical usefulness of continuous administration ofNocardia rubra cell wall skeleton (N-CWS) in diffuse panbronchiolitis (DPB)

Eight patients with diffuse panbronchiolitis (DPB) who had repeated intractable airway infections were continuously treated withNocardia rubra cell wall skeleton (N-CWS), a biological response modifier. As a result, subjective symptoms were reduced in 6 patients. Antibiotics therapy could be discontinued completely in two patients and the dose of antibiotics could be reduced considerably in two other patients. No adverse reactions in relation to N-CWS were observed. These results suggest that N-CWS is effective in treating erythromycin-resistant DPB.Abbreviations BRM Biological response modifier - DPB Diffuse panbronchiolitis - EM erythromycin - N-CWS Nocardia rubra cell wall skeleton     

Defective in vitro production of influenza virus-specific cytotoxic T lymphocytes in ataxia-telangiectasia

Peripheral blood mononuclear cells (PBMC) from patients with ataxia-telangiectasia (A-T) were studied for their capacity to proliferate and to generate influenza virus-specific cytotoxic T lymphocytes (CTL) after in vitro stimulation with influenza A/Hong Kong (A/HK (H3N2)) virus. PBMC from 11 patients proliferated poorly to A/HK and 10 of the 11 patients failed to exhibit significant CTL effector activity when tested on influenza A/HK virus-infected autologous target cells. In contrast, PBMC from each of 18 simultaneously studied, unrelated normal individuals proliferated to A/HK and generated influenza-immune CTL. In each of the 10 A-T patients, deficient CTL activity was shown to be due to a lack of generation of CTL and not to target cell resistance to lysis, because the virtually infected target cells of the patients were lysed by parental influenza-immune CTL. Determinations of T cell numbers and existing serum antibody titers to H3N2 influenza virus suggest this nonresponsiveness cannot be simply explained by a lack of T cells or the absence of exposure to type A (H3N2) influenza virus. Studies in which CTL were generated in A-T plasmas and during co-culture of PBMC from an A-T patient and an MHC-matched sibling failed to demonstrate either plasma or cellular suppression as a mechanism for the lack of CTL production in A-T patients. This immune defect in the production of cytotoxic effector T cells may be a cause of the increased frequency of infections and neoplasms observed in A-T patients.     

Immunomodulatory effects of bovine colostrum in human peripheral blood mononuclear cells

Human and bovine colostrum (BC) contain a remarkable amount of bioactive substances, including antibodies towards many common pathogens of the intestinal and respiratory tract as well as growth factors, vitamins, cytokines and other proteic, lipidic and glucidic factors. In this study we investigated whether BC had any immunomodulatory effect on human peripheral blood mononuclear cells (PBMC) from healthy donors. To this aim we focused on the production of IL-12 and IFN-gamma, cytokines involved in the Th1 polarization required for a successful immune response towards intracellular pathogens, such as bacteria and viruses. BC induced a dose-dependent production of IL-12 by CD14+ monocytes, but was unable to induce IFN-gamma production. However, BC differentially affected stimuli-induced IFN-gamma production: it enhanced IFN-gamma in response to weak antigenic stimulation and it inhibited IFN-gamma in response to strong antigenic stimulation. These effects were not dose-dependent. We also measured PBMC proliferation, which was substantially unaffected by BC. Our data suggest that the Th1-promoting activity of BC could contribute, together with the antibodies, to the protective effect of BC on the offspring. BC could also represent an inexpensive therapeutic tool in prevention and treatment of several human microbial infections, including influenza.     

Serologic studies of acute respiratory infections in military personnel.

The advantages, disadvantages, and uses of serological epidemiology are discussed in relation to acute respiratory infections in military personnel. The prevalence of antibody reflects both current and past experience with respiratory agents and is a measure of susceptinility. Incidence data calculated by testing two serial serum samples, on entry and discharge from the service, has indicated high influenza and mycoplasma pneumoniae rates in South American recruits and low rates of adenovirus and parainfluenza infections. Serologic analysis of reinfection rates showed high protection against influenza infections at HI antibody levels of over 1:40, against adenovirus infections at neutralizing titers of 1:5, and against M. pneumoniae infections at TRI antibody levels over 1:8. Antibody responses persisting at least 7 mo following immunization were demonstrated in 70% of 428 vaccinated young adults for A2 antigen and 20% for influenza B antigen. No relation of ABO blood groups to respiratory infection was found. The lack of myxovirus infections in four Polaris submarines is presented.     

Immunoglobulin Classes of Serum Antibodies Formed in Response to Natural Infections with Myxo- and Pseudomyxoviruses among Infants and Children

The occurrence of immunoglobulin classes of serum antibody in response to natural infections with myxo- and pseudomyxoviruses among infants and children was investigated. Two types of the 19S antibody response have been demonstrated. In the first type, in which are included the measles and mumps virus infections, the 19S antibody appeared dominantly as a primary response to the virus infection. In the second type, which includes the influenza, parainfluenza and RS virus infections, the 19S antibody was either not detectable or produced in a limiting amount in infants even at an early stage of the illnesses. A possibility was discussed that production of the 19S antibody in response to the infection with myxo- and pseudomyxoviruses may be primarily determined by the nature of virus infection itself, particularly the presence or absence of a viremia.     

A Prospective Study of Romanian Agriculture Workers for Zoonotic Influenza Infections

Background

In this prospective study we sought to examine seroepidemiological evidence for acute zoonotic influenza virus infection among Romanian agricultural workers.

Methods

Sera were drawn upon enrollment (2009) and again at 12 and 24 months from 312 adult agriculture workers and 51 age-group matched controls. Participants were contacted monthly for 24 months and queried regarding episodes of acute influenza-like illnesses (ILI). Cohort members meeting ILI criteria permitted respiratory swab collections as well as acute and convalescent serum collection. Serologic assays were performed against 9 avian, 3 swine, and 3 human influenza viruses.

Results

During the two-year follow-up, a total of 23 ILI events were reported. Two subjects'' specimens were identified as influenza A by rRT-PCR. During the follow-up period, three individuals experienced elevated microneutralization antibody titers ≥1∶80 against three (one each) avian influenza viruses: A/Teal/Hong Kong/w312/97(H6N1), A/Hong Kong/1073/1999(H9N2), or A/Duck/Alberta/60/1976(H12N5). However, none of these participants met the criteria for poultry exposure. A number of subjects demonstrated four-fold increases over time in hemagglutination inhibition (HI) assay titers for at least one of the three swine influenza viruses (SIVs); however, it seems likely that two of these three responses were due to cross-reacting antibody against human influenza. Only elevated antibody titers against A/Swine/Flanders/1/1998(H3N2) lacked evidence for such confounding. In examining risk factors for elevated antibody against this SIV with multiple logistic regression, swine exposure (adjusted OR = 1.8, 95% CI 1.1–2.8) and tobacco use (adjusted OR = 1.8; 95% CI 1.1–2.9) were important predictors.

Conclusions

While Romania has recently experienced multiple incursions of highly pathogenic avian influenza among domestic poultry, this cohort of Romanian agriculture workers had sparse evidence of avian influenza virus infections. In contrast, there was evidence, especially among the swine exposed participants, of infections with human and one swine H3N2 influenza virus.     

Development of a live biotherapeutic throat spray with lactobacilli targeting respiratory viral infections

Respiratory viruses such as influenza viruses, respiratory syncytial virus (RSV), and coronaviruses initiate infection at the mucosal surfaces of the upper respiratory tract (URT), where the resident respiratory microbiome has an important gatekeeper function. In contrast to gut-targeting administration of beneficial bacteria against respiratory viral disease, topical URT administration of probiotics is currently underexplored, especially for the prevention and/or treatment of viral infections. Here, we report the formulation of a throat spray with live lactobacilli exhibiting several in vitro mechanisms of action against respiratory viral infections, including induction of interferon regulatory pathways and direct inhibition of respiratory viruses. Rational selection of Lactobacillaceae strains was based on previously documented beneficial properties, up-scaling and industrial production characteristics, clinical safety parameters, and potential antiviral and immunostimulatory efficacy in the URT demonstrated in this study. Using a three-step selection strategy, three strains were selected and further tested in vitro antiviral assays and in formulations: Lacticaseibacillus casei AMBR2 as a promising endogenous candidate URT probiotic with previously reported barrier-enhancing and anti-pathogenic properties and the two well-studied model strains Lacticaseibacillus rhamnosus GG and Lactiplantibacillus plantarum WCFS1 that display immunomodulatory capacities. The three strains and their combination significantly reduced the cytopathogenic effects of RSV, influenza A/H1N1 and B viruses, and HCoV-229E coronavirus in co-culture models with bacteria, virus, and host cells. Subsequently, these strains were formulated in a throat spray and human monocytes were employed to confirm the formulation process did not reduce the interferon regulatory pathway-inducing capacity. Administration of the throat spray in healthy volunteers revealed that the lactobacilli were capable of temporary colonization of the throat in a metabolically active form. Thus, the developed spray with live lactobacilli will be further explored in the clinic as a potential broad-acting live biotherapeutic strategy against respiratory viral diseases.     

Chronic nicotine inhibits inflammation and promotes influenza infection

Epidemiological data suggest an association between smoking, respiratory infections, and impaired wound healing. Inflammation is critical in the body's defense against pathogens and in the wound-healing process. Although nicotine is used to treat some inflammatory conditions, the mechanism of this action is largely unknown. To determine how nicotine affects inflammation, rats and mice were exposed to nicotine via miniosmotic pumps, and the inflammatory response to turpentine or influenza virus was assessed. Results showed that while nicotine suppressed the migration of leukocytes to the inflammation/infection site, it increased the influenza titer in the lung. The decreased inflammation correlated with lower chemotaxis/chemokinesis of peripheral blood mononuclear cells (PBMC) toward formyl-methionyl-leucyl-phenylalanine and monocyte chemoattractant protein-1 without affecting the density of their respective receptors. However, nicotine suppressed the chemokine-induced Ca(2+) response in PBMC, indicating impaired chemokine signaling. Thus, because nicotine suppresses leukocyte migration, it might contribute to the delayed wound healing and increased incidence of respiratory infections among smokers.     

Human peripheral blood mononuclear cells produce IgA anti-influenza virus antibody in a secondary in vitro antibody response

The function and immunoregulation of human IgA memory B cells producing anti-influenza virus antibody was analyzed in vitro in antigen-stimulated cultures. Peripheral blood mononuclear cells (PBMC) from seven of eight normal adult volunteers naturally immunized to influenza virus produced IgA anti-influenza virus antibody when stimulated in vitro with inactivated A/Aichi/68 [H3N2] influenza virus. This IgA antibody response was approximately one-eighth the IgG antibody response. PBMC from each of five patients with selective IgA deficiency failed to produce any measurable IgA antibody. When tonsillar mononuclear cells (TMC) were studied in a similar manner, a relatively higher IgA antibody response was obtained (one-third the IgG antibody) than with PBMC. Additional studies were undertaken to investigate the immunoregulation of this IgA antibody production and the relatively lower amount produced by PBMC than by TMC. Co-cultures of peripheral blood B cells with irradiated peripheral blood T cells (to possibly inactivate a radiosensitive IgA suppressor cell) did not result in a relative increase in IgA antibody production. Also, co-cultures of B cells with increasing numbers of T cells produced parallel increases of IgG and IgA antibody when plotted on a log scale with slopes of approximately 1, suggesting that a single helper T cell was limiting for both isotypes. Finally, pokeweed mitogen-stimulated co-cultures of peripheral blood and tonsillar B and T cells revealed that the B cell population, but not the T cell population, determined the amount of IgA anti-influenza virus antibody produced. Precursor frequency analyses of tonsillar and peripheral blood B cells in antigen-stimulated cultures confirmed that tonsils contained a higher precursor frequency of B cells for IgA anti-influenza virus antibody production (3.95/10(6) B cells) than did peripheral blood B cells (0.65/10(6) B cells). Thus, IgA memory cells are preferentially found in tonsillar tissue as compared with the peripheral blood, consistent with the role of the tonsils as a mucosal immune organ.     

Immunosuppression induced by respiratory viruses (influenza virus, adenovirus) in mice

The influence of respiratory viruses (adenovirus, influenza virus) on humoral immune response to heterologous T-dependent and T-independent antigens was studied. It was shown that inoculation of mice by the influenza virus (A/PR8/34-A/PR/8) 3 days before sheep red blood cells administration led to the inhibition of antibody forming cell (AFC) and immunoglobulin, forming cell (IFC) increase on 69% and 59% respectively. Adenovirus type 6 induced the similar suppression of AFC and IFC formation. Thus, viruses induced immuno-suppression, which was polyclonal. It was also shown that virus of one strain (type) could inhibit immune response to another strain (type) of virus. The immune response to T-independent antigen was not suppressed. The virus-induced immunosuppression was dependent on: 1) the infectivity of respiratory viruses, 2) the route of virus and heterologous antigen injection, and 3) the interval between the viruses and antigen inoculation.     

Therapeutic effect of anti-macrophage inflammatory protein 2 antibody on influenza virus-induced pneumonia in mice

We investigated the effect of anti-macrophage inflammatory protein 2 immunoglobulin G (aMIP-2 IgG) on the progression of influenza virus-induced pneumonia in mice. When mice were infected with a mouse lung-adapted strain of influenza A/PR/8/34 virus by intranasal inoculation, neutrophil counts in the bronchoalveolar lavage fluid (BALF) increased in parallel with the kinetics of MIP-2 production, which peaked 2 days after infection. After intracutaneous injection of a dose of 10 or 100 microg of aMIP-2 IgG once a day on days 0 and 1, neutrophil counts in BALF on day 2 were reduced to 49 or 37%, respectively, of the value in the control infected mice administered anti-protein A IgG. The antibody administration also improved lung pathology without affecting virus replication. Furthermore, by prolonged administration with a higher or lower dose for up to 5 days, body weight loss became slower and finally 40% of mice in both treatment groups survived potentially lethal pneumonia. These findings suggest that MIP-2-mediated neutrophil infiltration during the early phase of infection might play an important role in lung pathology. Thus, MIP-2 was considered to be a novel target for intervention therapy in potentially lethal influenza virus pneumonia in mice.     

Attenuation of inducible respiratory immune responses by oseltamivir treatment in mice infected with influenza A virus

The antiviral neuraminidase inhibitor oseltamivir (OSV) is widely used to suppress viral replication in the treatment of influenza. Here, we report that OSV administration significantly suppressed respiratory mucosal secretory IgA responses with respect to antigen (Ag)-specific antibody (Ab) production and also the induction of Ag-specific IgA Ab-forming cells, but not systemic IgG responses, in weanling mice as a model of pediatric influenza. Neutralizing activities of the airway fluids in oral OSV-treated mice were significantly less than those of sham-treated mice. Our findings suggest the risk of re-infection in patients showing a low mucosal response following OSV treatment.     

N-CWS灌胃对小鼠移植性肿瘤及免疫功能的影响

为了考察红色诺卡氏菌细胞壁骨架(Nocardia rubra cell wall skeleton,N-CWS)灌胃给药对小鼠的体内抑瘤效应及其免疫调节作用,采用小鼠肉瘤S_(180)的移植性肿瘤模型,检测N-CWS灌胃给药的抑瘤活性;同时观察N-CWS体内细胞毒作用和对正常小鼠的毒性、免疫器官重量、巨噬细胞(MΦ)吞噬功能及脾淋巴细胞转化的影响.结果显示,小鼠灌服N-CWS的LD_(50)＞1.2 g/kg;N-CWS 200、400、800 mg/kg剂量灌胃小鼠对S_(180)有明显的抑制作用,其抑瘤率分别为63.33%、71.11%、64.88%;与对照组比较,N-CWS可增加免疫器官重量和提升外周血白细胞数量、能明显提高小鼠MΦ的吞噬活性及显著提高淋巴细胞转化率(P＜0.05),同时N-CWS激活了的MΦ对肿瘤细胞的细胞毒效应亦明显增强(P＜0.05).因此N-CWS适用于口服给药,对小鼠移植性肿瘤有明显的抑制作用,其抗肿瘤作用可能与增强机体免疫功能有关.     

New Class of Monoclonal Antibodies against Severe Influenza: Prophylactic and Therapeutic Efficacy in Ferrets

Background

The urgent medical need for innovative approaches to control influenza is emphasized by the widespread resistance of circulating subtype H1N1 viruses to the leading antiviral drug oseltamivir, the pandemic threat posed by the occurrences of human infections with highly pathogenic avian H5N1 viruses, and indeed the evolving swine-origin H1N1 influenza pandemic. A recently discovered class of human monoclonal antibodies with the ability to neutralize a broad spectrum of influenza viruses (including H1, H2, H5, H6 and H9 subtypes) has the potential to prevent and treat influenza in humans. Here we report the latest efficacy data for a representative antibody of this novel class.

Methodology/Principal Findings

We evaluated the prophylactic and therapeutic efficacy of the human monoclonal antibody CR6261 against lethal challenge with the highly pathogenic avian H5N1 virus in ferrets, the optimal model of human influenza infection. Survival rates, clinically relevant disease signs such as changes in body weight and temperature, virus replication in lungs and upper respiratory tract, as well as macro- and microscopic pathology were investigated. Prophylactic administration of 30 and 10 mg/kg CR6261 prior to viral challenge completely prevented mortality, weight loss and reduced the amount of infectious virus in the lungs by more than 99.9%, abolished shedding of virus in pharyngeal secretions and largely prevented H5N1-induced lung pathology. When administered therapeutically 1 day after challenge, 30 mg/kg CR6261 prevented death in all animals and blunted disease, as evidenced by decreased weight loss and temperature rise, reduced lung viral loads and shedding, and less lung damage.

Conclusions/Significance

These data demonstrate the prophylactic and therapeutic efficacy of this new class of human monoclonal antibodies in a highly stringent and clinically relevant animal model of influenza and justify clinical development of this approach as intervention for both seasonal and pandemic influenza.     

Immunologic effects of interferon-alpha in man: treatment with human recombinant interferon-alpha suppresses in vitro immunoglobulin production in patients with chronic type B hepatitis

The effect of human recombinant interferon-alpha on lymphocyte proliferation and differentiation was studied in 18 patients with chronic type B hepatitis who were participating in a randomized controlled trial of interferon-alpha therapy. Peripheral blood mononuclear cells (PBMC) were obtained by lymphopheresis before and during a 4 mo course of interferon. Pokeweed mitogen-induced immunoglobulin synthesis by PBMC obtained from patients before therapy was similar to that of PBMC from normal individuals. However, after 2 wk treatment with human recombinant interferon-alpha mitogen-induced immunoglobulin production was decreased by an average of 50%. Staining for cytoplasmic immunoglobulin revealed decreases that paralleled secreted immunoglobulin, indicating that interferon-alpha treatment inhibited immunoglobulin synthesis. Mixing autologous T and B cell enriched populations from before and during interferon treatment revealed that the decrease in immunoglobulin synthesis involved a defect in the B cell-enriched population. In contrast to immunoglobulin synthesis, pokeweed mitogen-induced lymphocyte proliferation was not significantly affected by in vivo administration of interferon-alpha. Thus a major effect of in vivo interferon-alpha on immunoregulation in patients with chronic type B hepatitis appears to be an inhibition of the late stages of B cell differentiation into immunoglobulin producing and secreting plasma cells.     

Immunostimulant patch enhances immune responses to influenza virus vaccine in aged mice

Improvement in the immune response to influenza virus vaccination in the elderly represents the primary unmet need in influenza virus vaccination. We have shown that topical application of immunostimulating (IS) patches containing heat-labile enterotoxin of Escherichia coli (LT) enhances immune responses to injected vaccines. We extend these findings and show that LT-IS patch application enhances the antibody responses to influenza virus vaccination in both young and aged mice. LT-IS patches markedly increased influenza virus-specific immunoglobulin G (IgG), hemagglutination inhibition antibody, mucosal antibody, and T-cell responses. The magnitude of the immune responses in aged mice receiving an LT-IS patch was equivalent to or greater than that of the immune responses in young mice given vaccine alone. These results suggest that addition of an LT-IS patch may compensate for the deficient immune function seen in the aged in response to influenza virus vaccination. Therefore, use of an LT-IS patch could be a new, safe, and simple immunization strategy that may significantly improve the outcome of influenza virus vaccination in the elderly.     

Risk factors for lower respiratory complications of rhinovirus infections in elderly people living in the community: prospective cohort study.

OBJECTIVE: To assess the role of rhinoviruses in elderly people living in the community. DESIGN: Prospective community based surveillance of elderly people, without intervention. Subjects were telephoned weekly to identify symptomatic upper respiratory tract infections. Symptoms and impact of illnesses were monitored, and specimens were collected for diagnostic serology and human rhinovirus polymerase chain reaction. SETTING: Leicestershire, England. SUBJECTS: 533 subjects aged 60 to 90. MAIN OUTCOME MEASURES: Symptoms, restriction of activity, medical consultations, and antibiotic use during 96 rhinovirus infections. Adjusted odds ratios for lower respiratory syndromes with respect to smoking and health status. RESULTS: A viral cause was established in 211 (43%) of 497 respiratory illnesses; rhinoviruses were identified in 121 (24%) and as single pathogens in 107. The median duration of the first or only rhinovirus infection in the 96 people with 107 rhinovirus infections was 16 days; 18 of the 96 patients were confined to bed and 25 were unable to cope with routine household activities. Overall, 60 patients with rhinovirus infections had lower respiratory tract syndromes; 41 patients consulted their doctor, 31 of them (76%) receiving antibiotics. One patient died. Logistic regression analysis showed that chronic medical conditions increased the estimated probability of lower respiratory rhinovirus illness by 40% (95% confidence interval 17% to 68%) and smoking by 47% (14% to 90%). There were almost six times as many symptomatic rhinovirus infections as influenza A and B infections. CONCLUSIONS: Rhinoviruses are an important cause of debility and lower respiratory illness among elderly people in the community. Chronic ill health and smoking increase the likelihood of lower respiratory complications from such infections. The overall burden of rhinovirus infections in elderly people may approach that of influenza.     

The Effect of Age and Recent Influenza Vaccination History on the Immunogenicity and Efficacy of 2009–10 Seasonal Trivalent Inactivated Influenza Vaccination in Children

Background

There is some evidence that annual vaccination of trivalent inactivated influenza vaccine (TIV) may lead to reduced vaccine immunogenicity but evidence is lacking on whether vaccine efficacy is affected by prior vaccination history. The efficacy of one dose of TIV in children 6–8 y of age against influenza B is uncertain. We examined whether immunogenicity and efficacy of influenza vaccination in school-age children varied by age and past vaccination history.

Methods and Findings

We conducted a randomized controlled trial of 2009–10 TIV. Influenza vaccination history in the two preceding years was recorded. Immunogenicity was assessed by comparison of HI titers before and one month after receipt of TIV/placebo. Subjects were followed up for 11 months with symptom diaries, and respiratory specimens were collected during acute respiratory illnesses to permit confirmation of influenza virus infections. We found that previous vaccination was associated with reduced antibody responses to TIV against seasonal A(H1N1) and A(H3N2) particularly in children 9–17 y of age, but increased antibody responses to the same lineage of influenza B virus in children 6–8 y of age. Serological responses to the influenza A vaccine viruses were high regardless of vaccination history. One dose of TIV appeared to be efficacious against confirmed influenza B in children 6–8 y of age regardless of vaccination history.

Conclusions

Prior vaccination was associated with lower antibody titer rises following vaccination against seasonal influenza A vaccine viruses, but higher responses to influenza B among individuals primed with viruses from the same lineage in preceding years. In a year in which influenza B virus predominated, no impact of prior vaccination history was observed on vaccine efficacy against influenza B. The strains that circulated in the year of study did not allow us to study the effect of prior vaccination on vaccine efficacy against influenza A.     

IL-17A Promotes Pulmonary B-1a Cell Differentiation via Induction of Blimp-1 Expression during Influenza Virus Infection

B-1 cells play a critical role in early protection during influenza infections by producing natural IgM antibodies. However, the underlying mechanisms involved in regulating this process are largely unknown. Here we found that during influenza infection pleural cavity B-1a cells rapidly infiltrated lungs, where they underwent plasmacytic differentiation with enhanced IgM production. This process was promoted by IL-17A signaling via induction of Blimp-1 expression and NF-κB activation in B-1a cells. Deficiency of IL-17A led to severely impaired B-1a-derived antibody production in the respiratory tract, resulting in a deficiency in viral clearance. Transfer of B-1a-derived natural antibodies rescued Il17a ^-/- mice from otherwise lethal infections. Together, we identify a critical function of IL-17A in promoting the plasmacytic differentiation of B-1a cells. Our findings provide new insights into the mechanisms underlying the regulation of pulmonary B-1a cell response against influenza infection.