Host immunology and rational immunotherapy for carbapenem-resistant Klebsiella pneumoniae infection

Iwanaga, Naoki; Sandquist, Ivy; Wanek, Alanna; McCombs, Janet E.; Song, Kejing; Kolls, Jay K.

doi:10.1172/jci.insight.135591

Cited by 17 publications

(20 citation statements)

References 52 publications

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“…Further studies are required to determine whether ILC3s are required for clearance. Using single cell RNA sequencing, we determined IL-17+, IL-22+, and ICOS+ ILC3s are imperative to protection against carbapenem resistant K. pneumoniae in a murine challenge model (33). This study also demonstrated that lung burdens in Rag2/Il2rg -/mice can be significantly reduced through the addition of exogenous IL-22.…”

Section: Ilc3s In Bacterial Pneumoniamentioning

confidence: 86%

“…As not all ILC3s express ICOS, it is possible in the deficient background the balance between ICOS+ and ICOS-ILC3s is shifted, especially since the total population of ILC3s in the lung at rest is very low (19,20). Indeed, we have shown administration of a neutralizing anti-ICOS antibody to mice prior to bacterial infection resulted in a decrease in Icos expression as well as expression of Il17 and Il22 after infection with Klebsiella pneumoniae (33). In addition, ex vivo stimulation of ILC3s isolated from K. pneumoniae infected mice with ICOS ligand (ICOSL) resulted in proliferation of cells (33), indicating the ICOS : ICOSL pathway may be important in mediating ILC3 function and proliferation (Figure 1).…”

Section: Regulation Of Ilc3 In the Lungmentioning

confidence: 87%

“…Indeed, we have shown administration of a neutralizing anti-ICOS antibody to mice prior to bacterial infection resulted in a decrease in Icos expression as well as expression of Il17 and Il22 after infection with Klebsiella pneumoniae (33). In addition, ex vivo stimulation of ILC3s isolated from K. pneumoniae infected mice with ICOS ligand (ICOSL) resulted in proliferation of cells (33), indicating the ICOS : ICOSL pathway may be important in mediating ILC3 function and proliferation (Figure 1). Interestingly, mouse and human ILC2s express both ICOS and functional ICOSL (35) which can stimulate ICOS+ Treg cells (36), raising the possibility that a coordinated interplay could also exist between ILC3 and ICOSL-expressing ILC2.…”

Section: Regulation Of Ilc3 In the Lungmentioning

confidence: 98%

“…The inducible T cell costimulatory molecule (ICOS) may also stimulate ILC3s in the lung. Differential expression of ICOS, which is also expressed on T cells, has been observed in both mouse and human ILC3s (33,34). However, the role of this molecule in regulating ILC3 function remains to be fully determined.…”

Section: Regulation Of Ilc3 In the Lungmentioning

confidence: 99%

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Regulation and Function of ILC3s in Pulmonary Infections

2021

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Lower respiratory infections are among the leading causes of morbidity and mortality worldwide. These potentially deadly infections are further exacerbated due to the growing incidence of antimicrobial resistance. To combat these infections there is a need to better understand immune mechanisms that promote microbial clearance. This need in the context of lung infections has been further heightened with the emergence of SARS-CoV-2. Group 3 innate lymphoid cells (ILC3s) are a recently discovered tissue resident innate immune cell found at mucosal sites that respond rapidly in the event of an infection. ILC3s have clear roles in regulating mucosal immunity and tissue homeostasis in the intestine, though the immunological functions in lungs remain unclear. It has been demonstrated in both viral and bacterial pneumonia that stimulated ILC3s secrete the cytokines IL-17 and IL-22 to promote both microbial clearance as well as tissue repair. In this review, we will evaluate regulation of ILC3s during inflammation and discuss recent studies that examine ILC3 function in the context of both bacterial and viral pulmonary infections.

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Section: Ilc3s In Bacterial Pneumoniamentioning

confidence: 86%

Section: Regulation Of Ilc3 In the Lungmentioning

confidence: 87%

Section: Regulation Of Ilc3 In the Lungmentioning

confidence: 98%

Section: Regulation Of Ilc3 In the Lungmentioning

confidence: 99%

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Regulation and Function of ILC3s in Pulmonary Infections

2021

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“…Antibiotic resistance is a worldwide challenge for the treatment of bacterial pathogens and has led to the necessity for developing alternative medications. A recent study aimed to unravel the involved host factors responsible for carbapenem-resistant K. pneumoniae sequence type 258 (ST258) infection [ 136 ]. By using single cell RNA sequencing, the authors identified distinct clusters of IFN-γ-producing NK cells and Il17a + Il22 + ICOS + ILC3 to be critical for the host resistance in this infection.…”

Section: Infections Of the Lungmentioning

confidence: 99%

Innate Lymphoid Cells: Important Regulators of Host–Bacteria Interaction for Border Defense

2020

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Innate lymphoid cells (ILCs) are a recently discovered type of innate immune lymphocyte. They include three different groups classified by the nature of the transcription factors required for their development and by the cytokines they produce. ILCs mainly reside in tissues close to the mucosal barrier such as the respiratory and gastrointestinal tracts. Due to their close proximity to the mucosal surface, ILCs are exposed to a variety of both commensal and pathogenic bacteria. Under non-pathological conditions, ILCs have been shown to be important regulators for the maintenance of tissue homeostasis by mutual interactions with the microbiome. Besides these important functions at homeostasis, several studies have also provided emerging evidence that ILCs contribute to defense against pathogenic bacterial infection by responding rapidly to the pathogens as well as orchestrating other immune cells. In this review, we summarize recent advances in our understanding of the interactions of ILCs and bacteria, with special focus on the function of the different ILC subsets in bacterial infections.

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