Interferon α–Enhanced Clearance of Group A Streptococcus Despite Neutropenia

Uchiyama, Satoshi; Keller, Nadia; Schlaepfer, Erika; Grube, Christina; Schuepbach, Reto A.; Speck, Roberto F.

doi:10.1093/infdis/jiw157

Cited by 12 publications

(20 citation statements)

References 40 publications

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“…Conversely, the human but not mouse TLR8 appears to be involved in type I IFN induction by bacterial RNA (59). Some antimicrobial functions of human neutrophils are enhanced by type I IFNs (78) whereas such stimulatory effects have so far not been described in mouse neutrophils. Future work should put more emphasis on studies of common and distinct features of type I IFN functions in bacterial infections.…”

Section: Discussionmentioning

confidence: 99%

Type I Interferons in Bacterial Infections: A Balancing Act

et al. 2016

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Defense against bacterial infections requires activation of the immune response as well as timely reestablishment of tissue and immune homeostasis. Instauration of homeostasis is critical for tissue regeneration, wound healing, and host recovery. Recent studies revealed that severe infectious diseases frequently result from failures in homeostatic processes rather than from inefficient pathogen eradication. Type I interferons (IFN) appear to play a key role in such processes. Remarkably, the involvement of type I IFNs in the regulation of immune and tissue homeostasis upon bacterial insult may have beneficial or detrimental consequences for the host. The reasons for such ambivalent function of type I IFNs are not understood. The disparate effects of type I IFNs on bacterial infections are in marked contrast to their well-established protective roles in most viral infections. In this review, we will focus on type I IFN effector mechanisms which balance processes involved in immune and tissue homeostasis during specific bacterial infections and highlight the most important missing links in our understanding of type I IFN functions.

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Section: Discussionmentioning

confidence: 99%

Type I Interferons in Bacterial Infections: A Balancing Act

et al. 2016

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“…For example, in vivo studies in mice indicate that S. aureus -triggered type I IFNs can be detrimental ( 45 ). On the other hand, type I IFN signaling is required to control disease and increase survival rate after other pathogenic bacterial infections, including Group A streptococci ( 46 ), Group B streptococci, pneumococci, E. coli ( 47 ), and Streptococcus pyogenes ( 48 ). In cattle, a single study reported that S. uberis could upregulate the transcription of IFN-ω ( 49 ).…”

Section: Discussionmentioning

confidence: 99%

Differential Ability of Bovine Antimicrobial Cathelicidins to Mediate Nucleic Acid Sensing by Epithelial Cells

Baumann¹,

Kiener²,

Haigh

et al. 2017

Front. Immunol.

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Cathelicidins encompass a family of cationic peptides characterized by antimicrobial activity and other functions, such as the ability to enhance the sensing of nucleic acids by the innate immune system. The present study aimed to investigate the ability of the bovine cathelicidins indolicidin, bactenecin (Bac)1, Bac5, bovine myeloid antimicrobial peptide (BMAP)-27, BMAP-28, and BMAP-34 to inhibit the growth of bacteria and to enhance the sensing of nucleic acid by the host’s immune system. BMAP-27 was the most effective at killing Staphylococcus aureus, Streptococcus uberis, and Escherichia coli, and this was dependent on its amphipathic structure and cationic charge. Although most cathelicidins possessed DNA complexing activity, only the alpha-helical BMAP cathelicidins and the cysteine-rich disulfide-bridged Bac1 were able to enhance the sensing of nucleic acids by primary epithelial cells. We also compared these responses with those mediated by neutrophils. Activation of neutrophils with phorbol myristate acetate resulted in degranulation and release of cathelicidins as well as bactericidal activity in the supernatants. However, only supernatants from unstimulated neutrophils were able to promote nucleic acid sensing in epithelial cells. Collectively, the present data support a role for certain bovine cathelicidins in helping the innate immune system to sense nucleic acids. The latter effect is observed at concentrations clearly below those required for direct antimicrobial functions. These findings are relevant in development of future strategies to promote protection at mucosal surfaces against pathogen invasion.

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“…However, P levels did not appear to drop further in persons with more prolonged neutropenia, suggesting that cells other than neutrophils contribute significantly to P synthesis. Indeed, T cells and monocytes/macrophages also synthesize P [9–11, 20] and could contribute to the pool of circulating P in the absence of neutrophils. An alternative explanation is that the half-life for P is long.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, the effects of lower P levels and the resulting decrease in C3 convertase stability are likely to be manifest at lower serum concentrations. Uchiyama et al [20] recently reported that individuals receiving interferon (IFN)-α treatment for hepatitis C had increased P levels compared with pre- or posttreatment levels. They demonstrated that treating monocytes and neutrophils with IFN-α resulted in increased P release from these cells in culture.…”

Section: Discussionmentioning

confidence: 99%

Properdin Levels in Individuals with Chemotherapy-Induced Neutropenia

Tsyrkunou

Agarwal

Koirala

et al. 2016

Open Forum Infectious Diseases

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Background.Neutrophils produce and carry key components of the alternative pathway (AP) of complement, including properdin (P). The effect of chemotherapy-induced absolute neutropenia on circulating P levels and AP function has not been previously established.Methods.We prospectively measured free P levels in serum from 27 individuals expected to develop neutropenia after administration of chemotherapy for hematological malignancies in preparation for hematopoietic stem cell transplantation and here describe the relationship between serum P levels and the neutrophil count over time.Results.When the absolute neutrophil count (ANC) was >500 cells/mm3 pre-chemotherapy, P levels were significantly higher than P levels associated with an ANC ≤500 cells/mm3 (median values 8392 ng/mL and 6355 ng/mL, respectively; P = .001). Pairwise comparison between pre-chemotherapy P levels and P levels at initial or last documented neutropenia before recovery showed a significant decline (P < .0001). No correlation was observed between P levels during neutropenia and after recovery of neutropenia in 20 subjects for which postneutropenia samples were obtained. A small but significant (P = .02) decrease in AP hemolytic activity was noted between baseline (preneutropenia) and samples obtained at the onset of neutropenia, but only with low (6.25%) and not higher (12.5 or 25%) serum concentrations.Conclusions.A decline in P levels and AP activity could contribute to the increased risk of infection in neutropenic patients and warrants further study.

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Interferon α–Enhanced Clearance of Group A Streptococcus Despite Neutropenia

Abstract: These findings help to explain the rather discrepant facts of neutropenia but preserved antibacterial immune defenses in patients treated with IFN-α.

Cited by 12 publications

References 40 publications

Type I Interferons in Bacterial Infections: A Balancing Act

Type I Interferons in Bacterial Infections: A Balancing Act

Differential Ability of Bovine Antimicrobial Cathelicidins to Mediate Nucleic Acid Sensing by Epithelial Cells

Properdin Levels in Individuals with Chemotherapy-Induced Neutropenia

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