Ageing and the neutrophil: no appetite for killing?

Butcher, Stephen K.; Chahel, H.; Lord, Janet M.

doi:10.1046/j.1365-2567.2000.00079.x

Cited by 179 publications

(138 citation statements)

References 46 publications

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“…Of these two components, recent evidence suggests that the process of phagocytosis acts immediately upon infection and clears the majority of pathogens (Haine et al 2008) while AMP production plays a relatively minor role in bacterial clearance. Age-related declines in the efficiency of phagocytosis have been reported in other organisms (Fearon and Locksley 1996;Butcher et al 2000Butcher et al , 2001Ginaldi et al 2001;DeVeale et al 2004;Terrón et al 2004;Panda et al 2009) and also in Drosophila (Mackenzie et al 2011). Recent evidence also suggests that the number of blood cells (phagocytes) declines with age in Drosophila (Mackenzie et al 2011).…”

Section: Discussionmentioning

confidence: 84%

Age-Specific Variation in Immune Response inDrosophila melanogasterHas a Genetic Basis

et al. 2012

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Immunosenescence, the age-related decline in immune system function, is a general hallmark of aging. While much is known about the cellular and physiological changes that accompany immunosenescence, we know little about the genetic influences on this phenomenon. In this study we combined age-specific measurements of bacterial clearance ability following infection with whole-genome measurements of the transcriptional response to infection and wounding to identify genes that contribute to the natural variation in immunosenescence, using Drosophila melanogaster as a model system. Twenty inbred lines derived from nature were measured for their ability to clear an Escherichia coli infection at 1 and 4 weeks of age. We used microarrays to simultaneously determine genome-wide expression profiles in infected and wounded flies at each age for 12 of these lines. Lines exhibited significant genetically based variation in bacterial clearance at both ages; however, the genetic basis of this variation changed dramatically with age. Variation in gene expression was significantly correlated with bacterial clearance ability only in the older age group. At 4 weeks of age variation in the expression of 247 genes following infection was associated with genetic variation in bacterial clearance. Functional annotation analyses implicate genes involved in energy metabolism including those in the insulin signaling/TOR pathway as having significant associations with bacterial clearance in older individuals. Given the evolutionary conservation of the genes involved in energy metabolism, our results could have important implications for understanding immunosenescence in other organisms, including humans.

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Section: Discussionmentioning

confidence: 84%

Age-Specific Variation in Immune Response inDrosophila melanogasterHas a Genetic Basis

et al. 2012

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“…Arguing against this proposal in the case of ageing of PMN, were the findings of Chatta et al [45] and Born et al [18] indicating that the proliferative and differentiation capacity of hematopoietic progenitor cells was largely unaffected by ageing in humans. However, the ability of progenitors to proliferate and differentiate in response to hematopoietic factors does not necessarily guarantee that the resulting PMN are competent [35]. Inflammation and infection do increase the rate of PMN production, shortening the maturation time and leading to the release of immature immune cells in the circulation.…”

Section: Ageing Of Pmnmentioning

confidence: 99%

Severity of E. coli mastitis is mainly determined by cow factors

et al. 2003

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-Intramammary infections of dairy cows with Gram-positive bacteria such as Staphylococcus aureus (major cause of mastitis) have received a lot of attention because of their major economic impact on the dairy farm through production losses induced by an increase in somatic cell count. Management strategies, including greater awareness for efficient milking and hygienic measures, have limited the spread of Gram-positive bacteria and resulted in a significant decrease of proportion of S. aureus isolates and subclinical mastitis worldwide. Other organisms such as coliform subspecies and Streptococcus uberis, both environmental bacteria that cause clinical mastitis, have received less attention. Escherichia coli causes inflammation of the mammary gland in dairy cows around parturition and during early lactation with striking local and sometimes severe systemic clinical symptoms. This disease affects many high producing cows in dairy herds and may cause several cases of death per year in the most severe cases. It is well known that bacterial, cow and environmental factors are interdependent and influence mastitis susceptibility. Many studies, executed during the last decade, indicate that the severity of E. coli mastitis is mainly determined by cow factors rather than by E. coli pathogenicity. During E. coli mastitis, the host defense status is a cardinal factor determining the outcome of the disease. Today, we know that the neutrophil is a key factor in the cows' defense against intramammary infection with E. coli. Effective elimination of the pathogen by neutrophils is important for the resolution of infection and the outcome of E. coli mastitis. This review is a compilation of some major findings over the last 15 years concerning mainly host factors that modulate and influence neutrophil function and the mammary inflammatory reaction. The individual chapters address: virulence factors of E. coli strains, how neutrophils kill E. coli, connection between endotoxins, tumor necrosis factor-a and nitric oxide, severity classification of E. coli mastitis, lifespan of neutrophils, host factors that influence severity, tissue damage and production loss.

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“…Periodontitis and other infection-driven chronic inflammatory diseases generally appear rather late in life, but it is not clear whether, or what kind of, age-related alterations in innate immune function are responsible. Interestingly, although phagocytosis generally declines with aging (Sebastian et al, 2005;Butcher et al, 2000), CR3 (CD11b/CD18)-dependent phagocytosis is intact (Butcher et al, 2001). Specifically, unlike FcγRIIIa (CD16)-mediated phagocytosis which declines because of age-related downregulation of CD16 expression, CD11b expression is preserved at old age (Butcher et al, 2001).…”

Section: In Vivo Evidence For Cr3 Exploitation By P Gingivalis and Imentioning

confidence: 99%

Subversion of Innate Immunity by Periodontopathic Bacteria via Exploitation of Complement Receptor-3

Hajishengallis

Wang²,

Liang³

et al. 2008

Advances in Experimental Medicine and Biology

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The capacity of certain pathogens to exploit innate immune receptors enables them to undermine immune clearance and persist in their host, often causing disease. Here we review subversive interactions of Porphyromonas gingivalis, a major periodontal pathogen, with the complement receptor-3 (CR3; CD11b/CD18) in monocytes/macrophages. Through its cell surface fimbriae, P. gingivalis stimulates Toll-like receptor-2 (TLR2) inside-out signaling which induces the highaffinity conformation of CR3. Although this activates CR3-dependent monocyte adhesion and transendothelial migration, P. gingivalis has co-opted this TLR2 proadhesive pathway for CR3 binding and intracellular entry. In CR3-deficient macrophages, the internalization of P. gingivalis is reduced 2-fold but its ability to survive intracellularly is reduced 1000-fold, indicating that CR3 is exploited by the pathogen as a relatively safe portal of entry. The interaction of P. gingivalis fimbriae with CR3 additionally inhibits production of bioactive (p70) interleukin-12, which mediates immune clearance. In vivo blockade of CR3 leads to reduced persistence of P. gingivalis in the mouse host and diminished ability to cause periodontal bone loss, the hallmark of periodontal disease. Strikingly, the ability of P. gingivalis to interact with and exploit CR3 depends upon quantitatively minor components (FimCDE) of its fimbrial structure, which predominantly consists of polymerized fimbrillin (FimA). Indeed, isogenic mutants lacking FimCDE but expressing FimA are dramatically less persistent and virulent than the wild-type organism both in vitro and in vivo. This model of immune evasion through CR3 exploitation by P. gingivalis supports the concept that pathogens evolved to manipulate innate immune function for promoting their adaptive fitness.

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Ageing and the neutrophil: no appetite for killing?

Cited by 179 publications

References 46 publications

Age-Specific Variation in Immune Response inDrosophila melanogasterHas a Genetic Basis

Age-Specific Variation in Immune Response inDrosophila melanogasterHas a Genetic Basis

Severity of E. coli mastitis is mainly determined by cow factors

Subversion of Innate Immunity by Periodontopathic Bacteria via Exploitation of Complement Receptor-3

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