T Cell Memory Response to Pneumococcal Protein Antigens in an Area of High Pneumococcal Carriage and Disease

Mureithi, Marianne; Finn, Adam; Ota, Martin O. C.; Zhang, Qibo; Davenport, Victoria; Mitchell, Tim; Williams, Neil; Adegbola, Richard A.; Heyderman, Robert S.

doi:10.1086/605023

Cited by 51 publications

(62 citation statements)

References 47 publications

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“…In fact, we have previously shown that, while pneumolysin triggers IL-1␤ secretion in murine DCs, it inhibits IL-1␤ in human DCs (15). Furthermore, in agreement with our study, Mureithi and colleagues found that, although recombinant pneumolysin could induce IFN-␥ and IL-17 from human PBMCs, the responses seen with the wild type and a pneumolysin-deficient mutant did not differ (25).…”

Section: Discussionsupporting

confidence: 92%

“…Interestingly, Kemp et al found that IFN-␥-producing T cells disappear from the circulation in patients with pneumococcal pneumonia or bacteremia, suggesting that these cells are engaged in the in vivo immune response (10). Furthermore, it has been demonstrated that peripheral blood mononuclear cells (PBMCs) from healthy adults living in a region with a high incidence of pneumococcal carriage and disease respond to pneumococcal antigens with both IFN-␥ and IL-17 production, indicating that exposure to pneumococci results in T cell-mediated immunological memory (25).…”

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confidence: 99%

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Human Monocytes Promote Th1 and Th17 Responses to Streptococcus pneumoniae

et al. 2011

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Streptococcus pneumoniae is a leading cause of bacterial pneumonia, meningitis, and sepsis in children. Human immunity to pneumococcal infections has been assumed to depend on anticapsular antibodies. However, recent findings from murine models suggest that alternative mechanisms, dependent on T helper cells, are also involved. Although the immunological events in which T helper cells contribute to acquired immunity have been studied in mice, little is known about how these responses are generated in humans. Therefore, we examined bacterial and host factors involved in the induction of Th1 and Th17 responses, using a coculture model of human monocytes and CD4 ؉ T cells. We show that monocytes promote effector cytokine production by memory T helper cells, leading to a mixed Th1/Th17 (gamma interferon [IFN-␥]/interleukin-17 [IL-17])profile. Both T helper cytokines were triggered by purified pneumococcal peptidoglycan; however, the balance between the two immune effector arms depended on bacterial viability. Accordingly, live pneumococci triggered a Th1-biased response via monocyte production of IL-12p40, whereas heat-killed pneumococci triggered a Th17 response through TLR2 signaling. An increased understanding of human T helper responses is essential for the development of novel pneumococcal vaccines designed to elicit cell-mediated immunity.

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Section: Discussionsupporting

confidence: 92%

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confidence: 99%

Human Monocytes Promote Th1 and Th17 Responses to Streptococcus pneumoniae

et al. 2011

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“…T and B lymphocytes were found to be attracted to the site of infection, and the absence of PLY caused overall reduced bacterial growth as well as reduced recruitment of lymphocytes in vivo (376). A clinical study of CD4-positive T cells from previously exposed people showed that PLY, although not immunodominant, causes a distinct proinflammatory, Th1 profile of high IFN-␥, IL-12, and IL-17 levels and low IL-10 and IL-13 levels (377).…”

Section: Adaptive Immune Responses To Pftsmentioning

confidence: 99%

Role of Pore-Forming Toxins in Bacterial Infectious Diseases

Los

Randis

Aroian

et al. 2013

Microbiol Mol Biol Rev

347

351

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SUMMARY Pore-forming toxins (PFTs) are the most common bacterial cytotoxic proteins and are required for virulence in a large number of important pathogens, including Streptococcus pneumoniae , group A and B streptococci, Staphylococcus aureus , Escherichia coli , and Mycobacterium tuberculosis . PFTs generally disrupt host cell membranes, but they can have additional effects independent of pore formation. Substantial effort has been devoted to understanding the molecular mechanisms underlying the functions of certain model PFTs. Likewise, specific host pathways mediating survival and immune responses in the face of toxin-mediated cellular damage have been delineated. However, less is known about the overall functions of PFTs during infection in vivo . This review focuses on common themes in the area of PFT biology, with an emphasis on studies addressing the roles of PFTs in in vivo and ex vivo models of colonization or infection. Common functions of PFTs include disruption of epithelial barrier function and evasion of host immune responses, which contribute to bacterial growth and spreading. The widespread nature of PFTs make this group of toxins an attractive target for the development of new virulence-targeted therapies that may have broad activity against human pathogens.

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“…Pneumolysin has been described to activate innate immune cells by signalling through the NLRP3 inflammasome complex 34, resulting in a proinflammatory response that may attract pneumococcal ‐ specific T cells 35, and induce the development and activation of protective Th17 responses, in particular in the nasopharynx 36. While a few studies have reported on pneumolysin‐specific Th1 and Th17 responses in peripheral blood, these responses seem less apparent than responses in nasopharynx‐associated lymphoid tissue 21, 37. We postulate that, particularly in the neonatal period, the innate immune signalling properties ascribed to pneumolysin may predominate over that of T cell responses.…”

Section: Discussionmentioning

confidence: 99%

Cord blood Streptococcus pneumoniae-specific cellular immune responses predict early pneumococcal carriage in high-risk infants in Papua New Guinea

Francis

Richmond

Strickland

et al. 2016

Clinical and Experimental Immunology

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SummaryIn areas where Streptococcus pneumoniae is highly endemic, infants experience very early pneumococcal colonization of the upper respiratory tract, with carriage often persisting into adulthood. We aimed to explore whether newborns in high‐risk areas have pre‐existing pneumococcal‐specific cellular immune responses that may affect early pneumococcal acquisition. Cord blood mononuclear cells (CBMC) of 84 Papua New Guinean (PNG; high endemic) and 33 Australian (AUS; low endemic) newborns were stimulated in vitro with detoxified pneumolysin (dPly) or pneumococcal surface protein A (PspA; families 1 and 2) and compared for cytokine responses. Within the PNG cohort, associations between CBMC dPly and PspA‐induced responses and pneumococcal colonization within the first month of life were studied. Significantly higher PspA‐specific interferon (IFN)‐γ, tumour necrosis factor (TNF)‐α, interleukin (IL)‐5, IL‐6, IL‐10 and IL‐13 responses, and lower dPly‐IL‐6 responses were produced in CBMC cultures of PNG compared to AUS newborns. Higher CBMC PspA‐IL‐5 and PspA‐IL‐13 responses correlated with a higher proportion of cord CD4 T cells, and higher dPly‐IL‐6 responses with a higher frequency of cord antigen‐presenting cells. In the PNG cohort, higher PspA‐specific IL‐5 and IL‐6 CBMC responses were associated independently and significantly with increased risk of earlier pneumococcal colonization, while a significant protective effect was found for higher PspA‐IL‐10 CBMC responses. Pneumococcus‐specific cellular immune responses differ between children born in pneumococcal high versus low endemic settings, which may contribute to the higher risk of infants in high endemic settings for early pneumococcal colonization, and hence disease.

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T Cell Memory Response to Pneumococcal Protein Antigens in an Area of High Pneumococcal Carriage and Disease

Cited by 51 publications

References 47 publications

Human Monocytes Promote Th1 and Th17 Responses to Streptococcus pneumoniae

Human Monocytes Promote Th1 and Th17 Responses to Streptococcus pneumoniae

Role of Pore-Forming Toxins in Bacterial Infectious Diseases

Cord blood Streptococcus pneumoniae-specific cellular immune responses predict early pneumococcal carriage in high-risk infants in Papua New Guinea

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