The role of IL-32 in Bacillus Calmette-Guérin (BCG)-induced trained immunity in infections caused by different Leishmania spp.

Silva, Muriel Vilela Teodoro; Santos, Jéssica Cristina dos; Figueiredo, Ana Marina Barroso de; Teufel, Lisa U.; Pereira, Jonathas Xavier; Matos, Grazzielle Guimarães de; Pinto, Sebastião Alves; Netea, Mihai G.; Gomes, Rodrigo Saar; Joosten, Leo A. B.; Ribeiro‐Dias, Fátima

doi:10.1016/j.micpath.2021.105088

Cited by 13 publications

(18 citation statements)

References 90 publications

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“…IL32 increased in H3K4me3 signal at BCG9 and pre-BCG10, ATG16L2 and KDM4E were increased at pre- BCG10, and H3K4me3 near TLR4 , the receptor for LPS, was decreased at BCG9. IL-32 plays a crucial role in the induction of TI by BCG 32, 33 . ATG16L2 is involved in autophagy and KDM4E is an epigenetic enzyme which demethylates H3K9 and regulates trained immunity responses 36 .…”

Section: Resultsmentioning

confidence: 99%

Intravesical BCG in patients with non-muscle invasive bladder cancer induces trained immunity and decreases respiratory infections

Puffelen

Novakovic

Emst

et al. 2022

Preprint

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Bacillus Calmette-Guérin (BCG) is recommended as intravesical immunotherapy to reduce the risk of tumor recurrence in patients with non-muscle invasive bladder cancer (NMIBC). Currently, it is unknown whether intravesical BCG application induces trained immunity. Here, we found that intravesical BCG does induce trained immunity based on an increased production of TNF and IL-1β after heterologous ex-vivo stimulation of circulating monocytes 6-12 weeks after intravesical BCG treatment; and a 37% decreased risk (OR 0.63 (95% CI 0.40-1.01)) for respiratory infections in BCG-treated versus non-BCG-treated NMIBC patients. An epigenomics approach combining ChIP-sequencing and RNA-sequencing with in-vitro trained immunity experiments identified enhanced inflammasome activity in BCG-treated individuals. Finally, germline variation in genes that affect trained immunity was associated with recurrence and progression after BCG therapy in NMIBC, suggesting a link between trained immunity and oncological outcome.

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Section: Resultsmentioning

confidence: 99%

Intravesical BCG in patients with non-muscle invasive bladder cancer induces trained immunity and decreases respiratory infections

Puffelen

Novakovic

Emst

et al. 2022

Preprint

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“…Together, data suggest a crucial role of the IL-32γ–Th17–neutrophil axis in the control of experimental VL. As stated above, IL-32 appears to mediate the BCG-trained immunity, which confers protection against L. infantum to human monocytes/macrophages and IL-32γTg mice ( 87 ). However, data on the role of IL-32 in the course of human VL deserve investigation.…”

Section: Il-32 In Different Leishmaniasesmentioning

confidence: 96%

“…Similar results were reported for human BCG-vaccinated volunteers genotyped for IL32 SNP rs4786370, in which the bone marrow myeloid progenitor cells with CC genotype presented an association of IL-32 expression with increased metabolic gene expression, besides inflammation ( 86 ). BCG reportedly induces IL-32 ( 40 , 87 ), while BCG-trained monocytes exhibit enhanced capacity to kill L. braziliensis , L. amazonensis , and L. infantum through increased ROS production ( 86 ). Moreover, IL-32γTg mice trained with BCG exhibit resistance to L. braziliensis and L. infantum , and control of L. amazonensis dissemination.…”

Section: Il-32 In Different Leishmaniasesmentioning

confidence: 99%

“…Moreover, IL-32γTg mice trained with BCG exhibit resistance to L. braziliensis and L. infantum , and control of L. amazonensis dissemination. This was associated with increased inflammation ( 87 ). Data indicate that IL-32 serves as a determinant of gene expression profile at the level of bone marrow progenitors by mediating the trained immunity induced by β-glucan or BCG and conferring protection against leishmaniasis.…”

Section: Il-32 In Different Leishmaniasesmentioning

confidence: 99%

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A Critical Overview of Interleukin 32 in Leishmaniases

Ribeiro‐Dias

Oliveira

2022

Front. Immunol.

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Interleukin-32 (IL-32) has several immune regulatory properties, which have driven its investigation in the context of various diseases. IL-32 expression is reported to be induced in the lesions of patients with American tegumentary leishmaniasis (ATL) by the New World Leishmania spp. that are responsible for causing ATL and visceral leishmaniasis (VL). IL-32 expression may elevate the inflammatory process through the induction of pro-inflammatory cytokines and also via mechanisms directed to kill the parasites. The genetic variants of IL-32 might be associated with the resistance or susceptibility to ATL, while different isoforms of IL-32 could be associated with distinct T helper lymphocyte profiles. IL-32 also determines the transcriptional profile in the bone marrow progenitor cells to mediate the trained immunity induced by β-glucan and BCG, thereby contributing to the resistance against Leishmania. IL-32γ is essential for the vitamin D-dependent microbicidal pathway for parasite control. In this context, the present review report briefly discusses the data retrieved from the studies conducted on IL-32 in leishmaniasis in humans and mice to highlight the current challenges to understanding the role of IL-32 in leishmaniasis.

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“…For example, IL-1β appears to be a critical cytokine induced by BCG-training: in BCG-trained monocytes, IL-1β levels increased after restimulation conferring non-specific protection against yellow fever viremia ( 26 ). The antimicrobial cytokine IL-32, which is known to be involved in viral defense and capable of modulating cellular metabolism ( 28 ), has also been demonstrated to play a role in BCG trained immunity, presumably by activating the NOD2 signaling pathway ( 29 ) ( Figure 1 ).…”

Section: Immune Training Agents Employ Multiple Pathways To Induce Tr...mentioning

confidence: 99%

Trained Immunity: An Overview and the Impact on COVID-19

et al. 2022

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Effectively treating infectious diseases often requires a multi-step approach to target different components involved in disease pathogenesis. Similarly, the COVID-19 pandemic has become a global health crisis that requires a comprehensive understanding of Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) infection to develop effective therapeutics. One potential strategy to instill greater immune protection against COVID-19 is boosting the innate immune system. This boosting, termed trained immunity, employs immune system modulators to train innate immune cells to produce an enhanced, non-specific immune response upon reactivation following exposure to pathogens, a process that has been studied in the context of in vitro and in vivo clinical studies prior to the COVID-19 pandemic. Evaluation of the underlying pathways that are essential to inducing protective trained immunity will provide insight into identifying potential therapeutic targets that may alleviate the COVID-19 crisis. Here we review multiple immune training agents, including Bacillus Calmette-Guérin (BCG), β-glucan, and lipopolysaccharide (LPS), and the two most popular cell types involved in trained immunity, monocytes and natural killer (NK) cells, and compare the signaling pathways involved in innate immunity. Additionally, we discuss COVID-19 trained immunity clinical trials, emphasizing the potential of trained immunity to fight SARS-CoV-2 infection. Understanding the mechanisms by which training agents activate innate immune cells to reprogram immune responses may prove beneficial in developing preventive and therapeutic targets against COVID-19.

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The role of IL-32 in Bacillus Calmette-Guérin (BCG)-induced trained immunity in infections caused by different Leishmania spp.

Cited by 13 publications

References 90 publications

Intravesical BCG in patients with non-muscle invasive bladder cancer induces trained immunity and decreases respiratory infections

Intravesical BCG in patients with non-muscle invasive bladder cancer induces trained immunity and decreases respiratory infections

A Critical Overview of Interleukin 32 in Leishmaniases

Trained Immunity: An Overview and the Impact on COVID-19

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