Protective T cell immunity against respiratory syncytial virus is efficiently induced by recombinant BCG

Bueno, Susan M.; González, Pablo A.; Cautivo, Kelly M.; Mora, Jorge E.; Leiva, Eduardo; Tobar, Hugo E.; Fennelly, Glenn J.; Eugenín, Eliseo A.; Jacobs, William R.; Riedel, Claudia A.; Kalergis, Alexis M.

doi:10.1073/pnas.0806244105

Cited by 105 publications

(161 citation statements)

References 58 publications

(56 reference statements)

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“…39 Indeed, it has been reported that adoptive transfer of CD4 C T cells from immunized mice with a prototype vaccine consisting in a recombinant rBCG expressing hRSV N protein (rBCG-N-hRSV), resulted in a significant reduced viral load in the lungs after infection in recipient mice, thus providing a protective T H 1 antiviral response. 38 These data suggest that CD4 C T cells itself stimulated with the proper antigens in can significantly contribute to hRSV clearance.…”

Section: An Adequate Cd4mentioning

confidence: 99%

“…61 Furthermore, it has been demonstrated that transfer of hRSV-N-specific T cells also contribute to reduce viral immunopathology. 38,39 Moreover, memory T cells appear to be clinically important in protecting from severe diseases caused by hRSV reinfections. This notion is supported by the fact that minor symptoms are observed in populations of older children and young adults infected with hRSV, despite of defective responses in IgA B cell memory and in hRSV-specific serum.…”

Section: Both Memory Cd4mentioning

confidence: 99%

“…Furthermore, recombinant Bacillus Calmette-Gu erin (rBCG) vaccines have been developed using hRSV and hMPV antigens to provide a protective T H 1 response in mice. 31,38,39 In addition, antibody-mediated immunity is relevant for protection against both viruses. 40,41 For example, Palivizumab, an IgG1 humanized anti-F monoclonal antibody, is safe and effective when given in a prophylactic manner to children at risk of severe hRSV infection.…”

Section: Introductionmentioning

confidence: 99%

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Aberrant T cell immunity triggered by human Respiratory Syncytial Virus and human Metapneumovirus infection

et al. 2016

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Human Respiratory syncytial virus (hRSV) and human metapneumovirus (hMPV) are the two major etiological viral agents of lower respiratory tract diseases, affecting mainly infants, young children and the elderly. Although the infection of both viruses trigger an antiviral immune response that mediate viral clearance and disease resolution in immunocompetent individuals, the promotion of long-term immunity appears to be deficient and reinfection are common throughout life. A possible explanation for this phenomenon is that hRSV and hMPV, can induce aberrant T cell responses, which leads to exacerbated lung inflammation and poor T and B cell memory immunity. The modulation of immune response exerted by both viruses include different strategies such as, impairment of immunological synapse mediated by viral proteins or soluble factors, and the induction of pro-inflammatory cytokines by epithelial cells, among others. All these viral strategies contribute to the alteration of the adaptive immunity in order to increase the susceptibility to reinfections.In this review, we discuss current research related to the mechanisms underlying the impairment of T and B cell immune responses induced by hRSV and hMPV infection. In addition, we described the role each virulence factor involved in immune modulation caused by these viruses.

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Section: An Adequate Cd4mentioning

confidence: 99%

Section: Both Memory Cd4mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Aberrant T cell immunity triggered by human Respiratory Syncytial Virus and human Metapneumovirus infection

et al. 2016

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“…Globally, the World Health Organization estimates that RSV causes up to 64 million infections and 160,000 deaths annually (2). Repeated reinfections are very common, suggesting that adaptive immunity after RSV infection is inefficient and nonlasting (3). Therefore, the development of a vaccine or antiviral drugs against this virus is a public health priority.…”

Section: R Espiratory Syncytial Virus (Rsv)mentioning

confidence: 99%

“…Similar observations were made in mice immunized with recombinant vaccinia virus expressing the RSV-G protein (16). Thus, it is thought that a Th1-polarized T cell immune response would be required to overcome the RSV-induced pathogenesis and efficiently clear the virus (3,(17)(18)(19)(20).…”

Section: R Espiratory Syncytial Virus (Rsv)mentioning

confidence: 99%

Efficient Lung Recruitment of Respiratory Syncytial Virus-Specific Th1 Cells Induced by Recombinant Bacillus Calmette-Guérin Promotes Virus Clearance and Protects from Infection

Cautivo

Bueno

Cortés

et al. 2010

The Journal of Immunology

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Human metapneumovirus infection activates the TSLP pathway that drives excessive pulmonary inflammation and viral replication in mice

et al. 2015

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Human metapneumovirus (hMPV) is a leading cause of acute respiratory tract infections in children and the elderly. The mechanism by which this virus triggers an inflammatory response still remains unknown. Here, we evaluated whether the thymic stromal lymphopoietin (TSLP) pathway contributes to lung inflammation upon hMPV infection. We found that hMPV infection promotes TSLP expression both in human airway epithelial cells and in the mouse lung. hMPV infection induced lung infiltration of OX40L + CD11b + DCs. Mice lacking the TSLP receptor deficient mice (tslpr −/− ) showed reduced lung inflammation and hMPV replication. These mice displayed a decreased number of neutrophils as well a reduction in levels of thymus and activation-regulated chemokine/CCL17, IL-5, IL-13, and TNF-α in the airways upon hMPV infection. Furthermore, a higher frequency of CD4 + and CD8 + T cells was found in tslpr −/− mice compared to WT mice, which could contribute to controlling viral spread. Depletion of neutrophils in WT and tslpr −/− mice decreased inflammation and hMPV replication. Remarkably, blockage of TSLP or OX40L with specific Abs reduced lung inflammation and viral replication following hMPV challenge in mice. Altogether, these results suggest that activation of the TSLP pathway is pivotal in the development of pulmonary pathology and pulmonary hMPV replication.Keywords: Dendritic cells r hMPV r Inflammation r Neutrophils r OX40L r TSLP r Viral replication Additional supporting information may be found in the online version of this article at the publisher's web-site Correspondence: Dr. Alexis M. Kalergis e-mail: akalergis@bio.puc.cl * These authors contributed equally to this work.C 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu Eur. J. Immunol. 2015. 45: 1680-1695 Immunity to infection 1681 IntroductionHuman metapneumovirus (hMPV) is an enveloped virus that belongs to the Paramyxoviridae family, Pneumovirinae subfamily, and the Metapneumovirus genus. The hMPV genome consists of a 13.3-kb single-stranded, negative-sense RNA encoding eight messenger RNAs, which are transcribed directly from the viral genome and translated into nine different polypeptides [1,2]. hMPV was described for the first time in 2001 as a pathogen responsible for acute respiratory tract infections in children [3]. Today, hMPV is considered the second most relevant etiological agent of acute upper and lower respiratory tract infections in children, the elderly, and immunocompromised adults [4]. Furthermore, in young children, hMPV is the second most reported cause of bronchiolitis and pneumonia after human respiratory syncytial virus (hRSV), accounting for ß10% of pediatric hospitalizations related to acute respiratory tract infection [5][6][7]. In addition, hMPV is the cause of outbreaks of acute respiratory tract infections with more than 10% mortality in elderly patients [8,9]. Currently, neither safe-effective vaccines nor specific antiviral therapies are available for hMPV, although promising candidate vaccines have recently be...

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Protective T cell immunity against respiratory syncytial virus is efficiently induced by recombinant BCG

Abstract: Respiratory syncytial virus (RSV) is

Cited by 105 publications

References 58 publications

Aberrant T cell immunity triggered by human Respiratory Syncytial Virus and human Metapneumovirus infection

Aberrant T cell immunity triggered by human Respiratory Syncytial Virus and human Metapneumovirus infection

Efficient Lung Recruitment of Respiratory Syncytial Virus-Specific Th1 Cells Induced by Recombinant Bacillus Calmette-Guérin Promotes Virus Clearance and Protects from Infection

Human metapneumovirus infection activates the TSLP pathway that drives excessive pulmonary inflammation and viral replication in mice

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