Mucosal immunosenescence: new developments and vaccines to control infectious diseases

Fujihashi, Kohtaro; Kiyono, Hiroshi

doi:10.1016/j.it.2009.04.004

Cited by 102 publications

(74 citation statements)

References 83 publications

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“…Furthermore, the lack of effect of the probiotic treatment on the total levels of fecal IgA does not exclude the possibility for probiotic effects on the secretion of antigen-specific IgA. Indeed, the current evidence suggests that aging does not markedly affect the levels of total IgA synthesis in mucosa or serum; instead, the quality of secreted IgA in intestinal mucosa may be altered, as a result of alterations in the gut microbiota associated with aging (Fujihashi and Kiyono 2009). Elevated fecal calprotectin and β-defensin concentrations have been associated with local inflammatory diseases (Gaya and Mackenzie 2002;Kapel et al 2009).…”

Section: Discussionmentioning

confidence: 80%

“…Imbalance in the inflammatory and anti-inflammatory functions in aging may result in low-grade chronic inflammation, termed inflammaging, characterized by elevated basal levels of pro-inflammatory immune mediators (Franceschi et al 2007). Alterations in the mucosal immunity associated with aging have also been identified, including reduction in intestinal antigen-specific IgA antibody responses (Fujihashi and Kiyono 2009). Improvement of innate and mucosal immune functions in the elderly therefore has great potential for improving the health status in the elderly.…”

Section: Introductionmentioning

confidence: 99%

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Probiotic cheese containing Lactobacillus rhamnosus HN001 and Lactobacillus acidophilus NCFM® modifies subpopulations of fecal lactobacilli and Clostridium difficile in the elderly

Lahtinen

Forssten

Aakko

et al. 2011

AGE

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Aging is associated with alterations in the intestinal microbiota and with immunosenescence. Probiotics have the potential to modify a selected part of the intestinal microbiota as well as improve immune functions and may, therefore, be particularly beneficial to elderly consumers. In this randomized, controlled cross-over clinical trial, we assessed the effects of a probiotic cheese containing Lactobacillus rhamnosus HN001 and Lactobacillus acidophilus NCFM on the intestinal microbiota and fecal immune markers of 31 elderly volunteers and compared these effects with the administration of the same cheese without probiotics. The probiotic cheese was found to increase the number of L. rhamnosus and L. acidophilus NCFM in the feces, suggesting the survival of the strains during the gastrointestinal transit. Importantly, probiotic cheese administration was associated with a trend towards lower counts of Clostridium difficile in the elderly, as compared with the run-in period with the plain cheese. The effect was statistically significant in the subpopulation of the elderly who harbored C. difficile at the start of the study. The probiotic cheese was not found to significantly alter the levels of the major microbial groups, suggesting that the microbial changes conferred by the probiotic cheese were limited to specific bacterial groups. Despite that the administration of the probiotic cheese to the study population has earlier been shown to significantly improve the innate immunity of the elders, we did not observe measurable changes in the fecal immune IgA concentrations. No increase in fecal calprotectin and β-defensin concentrations suggests that the probiotic treatment did not affect intestinal inflammatory markers. In conclusion, the administration of probiotic cheese containing L. rhamnosus HN001 and L. acidophilus NCFM, was associated with specific changes in the intestinal microbiota, mainly affecting specific subpopulations of intestinal lactobacilli and C. difficile, but did not have significant effects on the major microbial groups or the fecal immune markers.

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Section: Discussionmentioning

confidence: 80%

Section: Introductionmentioning

confidence: 99%

Probiotic cheese containing Lactobacillus rhamnosus HN001 and Lactobacillus acidophilus NCFM® modifies subpopulations of fecal lactobacilli and Clostridium difficile in the elderly

Lahtinen

Forssten

Aakko

et al. 2011

AGE

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“…Detailed studies of mucosal immunosenescence in general have only been undertaken with mice; it appears that nasal immune function deteriorates with age, but at a rate similar to that of systemic immunity, whereas intestinal mucosal immunity "ages" at a higher rate (104). Murine studies have demonstrated impaired innate antipneumococcal nasal mucosal immunity with increasing age, primarily stemming from macrophage dysfunction (105).…”

Section: Mucosal Antipneumococcal Immunity Is Affected By Agingmentioning

confidence: 99%

Pneumococcal Capsular Polysaccharide Immunity in the Elderly

Adler

Ferreira

Gordon

et al. 2017

Clin Vaccine Immunol

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Immunity to pneumococcal infections is impaired in older people, and current vaccines are poorly protective against pneumococcal disease in this population. Naturally acquired immunity to pneumococcal capsular polysaccharides develops during childhood and is robust in young adults but deteriorates with advanced age. In particular, antibody levels and function are reduced in older people. Pneumococcal vaccines are recommended for people Ͼ65 years old. However, the benefits of polysaccharide and protein-conjugated vaccines in this population are small, because of both serotype replacement and incomplete protection against vaccine serotype pneumococcal disease. In this review, we overview the immune mechanisms by which naturally acquired and vaccine-induced pneumococcal capsular polysaccharide immunity declines with age, including altered colonization dynamics, reduced opsonic activity of antibodies (particularly IgM), and impaired mucosal immunity.

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“…However, nasal immunization failed to induce mucosal immune responses in aged (2-y-old) mice despite the presence of an intact NALT-induced systemic immune response when native cholera toxin was used as nasal adjuvant (14,15). Furthermore, effectiveness of the current licensed trivalent nasal vaccine FluMist, which consists of type A (H1N1 and H3N2) and type B live attenuated influenza virus strains, has only been demonstrated in people 2-49 y of age (16). In this regard, it is essential to develop a new generation of mucosal adjuvants that are effective in the elderly.…”

Section: †mentioning

confidence: 99%

A Combination of Flt3 Ligand cDNA and CpG Oligodeoxynucleotide as Nasal Adjuvant Elicits Protective Secretory-IgA Immunity to Streptococcus pneumoniae in Aged Mice

Fukuyama

King

Kataoka

et al. 2011

The Journal of Immunology

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Our previous study showed that a combination of a plasmid-expressing Flt3 ligand (pFL) and CpG oligodeoxynucleotides (CpG ODN) as a combined nasal adjuvant elicited mucosal immune responses in aged (2-y-old) mice. In this study, we investigated whether a combination of pFL and CpG ODN as a nasal adjuvant for a pneumococcal surface protein A (PspA) would enhance PspA-specific secretory-IgA Ab responses, which could provide protective mucosal immunity against Streptococcus pneumoniae infection in aged mice. Nasal immunization with PspA plus a combination of pFL and CpG ODN elicited elevated levels of PspA-specific secretory-IgA Ab responses in external secretions and plasma in both young adult and aged mice. Significant levels of PspA-specific CD4+ T cell proliferative and PspA-induced Th1- and Th2- type cytokine responses were noted in nasopharyngeal-associated lymphoreticular tissue, cervical lymph nodes, and spleen of aged mice, which were equivalent to those in young adult mice. Additionally, increased numbers of mature-type CD8, CD11b-expressing dendritic cells were detected in mucosal inductive and effector lymphoid tissues of aged mice. Importantly, aged mice given PspA plus a combination of pFL and CpG ODN showed protective immunity against nasal S. pneumoniae colonization. These results demonstrate that nasal delivery of a combined DNA adjuvant offers an attractive possibility for protection against S. pneumoniae in the elderly.

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Mucosal immunosenescence: new developments and vaccines to control infectious diseases

Cited by 102 publications

References 83 publications

Probiotic cheese containing Lactobacillus rhamnosus HN001 and Lactobacillus acidophilus NCFM® modifies subpopulations of fecal lactobacilli and Clostridium difficile in the elderly

Probiotic cheese containing Lactobacillus rhamnosus HN001 and Lactobacillus acidophilus NCFM® modifies subpopulations of fecal lactobacilli and Clostridium difficile in the elderly

Pneumococcal Capsular Polysaccharide Immunity in the Elderly

A Combination of Flt3 Ligand cDNA and CpG Oligodeoxynucleotide as Nasal Adjuvant Elicits Protective Secretory-IgA Immunity to Streptococcus pneumoniae in Aged Mice

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