IL-33–mediated Eosinophilia Protects against Acute Lung Injury

Krishack, Paulette A.; Hollinger, Maile K.; Kuzel, Timothy G; Decker, T.; Louviere, Tyler J; Hrusch, Cara L.; Sperling, Anne I.; Verhoef, Philip A.

doi:10.1165/rcmb.2020-0166oc

Cited by 23 publications

(21 citation statements)

References 47 publications

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“…Krishack et al. ( 62 ) revealed that eosinophilia was critical for the protection against Staphylococcus aureus , which further suggested a potential protective effect of eosinophilia against bacterial infection. Thus, we inferred that moderate infiltration of eosinophils in the lung tissues after B. pertussis challenge may contribute to the aP+Al(OH) 3 /IP protection mechanism, except for the high level of antibodies.…”

Section: Discussionmentioning

confidence: 99%

Intranasal Immunization With a c-di-GMP-Adjuvanted Acellular Pertussis Vaccine Provides Superior Immunity Against Bordetella pertussis in a Mouse Model

Jiang

Wang

et al. 2022

Front. Immunol.

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Pertussis, caused by the gram-negative bacterium Bordetella pertussis, is a highly contagious respiratory disease. Intranasal vaccination is an ideal strategy to prevent pertussis, as the nasal mucosa represents the first-line barrier to B. pertussis infection. The current intramuscular acellular pertussis (aP) vaccines elicit strong antibody and Th2-biased responses but not necessary cellular and mucosal immunity. Here, we formulated two cyclic dinucleotide (CDN)-adjuvanted aP subunit vaccines, a mammalian 2’,3’-cGAMP-adjuvanted aP vaccine and a bacterial-derived c-di-GMP-adjuvanted aP vaccine, and evaluated their immunogenicity in a mouse model. We found that the aP vaccine alone delivered intranasally (IN) induced moderate systemic and mucosal humoral immunity but weak cellular immunity, whereas the alum-adjuvanted aP vaccine administered intraperitoneally elicited higher Th2 and systemic humoral immune responses but weaker Th1 and Th17 and mucosal immune responses. In contrast, both CDN-adjuvanted aP vaccines administered via the IN route induced robust humoral and cellular immunity systemically and mucosally. Furthermore, the c-di-GMP-adjuvanted aP vaccine generated better antibody production and stronger Th1 and Th17 responses than the 2′,3′-cGAMP-adjuvanted aP vaccine. In addition, following B. pertussis challenge, the group of mice that received IN immunization with the c-di-GMP-adjuvanted aP vaccine showed better protection than all other groups of vaccinated mice, with decreased inflammatory cell infiltration in the lung and reduced bacterial burden in both the upper and lower respiratory tracts. In summary, the c-di-GMP-adjuvanted aP vaccine can elicit a multifaceted potent immune response resulting in robust bacterial clearance in the respiratory tract, which indicates that c-di-GMP can serve as a potential mucosal adjuvant for the pertussis vaccine.

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Section: Discussionmentioning

confidence: 99%

Intranasal Immunization With a c-di-GMP-Adjuvanted Acellular Pertussis Vaccine Provides Superior Immunity Against Bordetella pertussis in a Mouse Model

Jiang

Wang

et al. 2022

Front. Immunol.

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“…Zhu et al 11 found that CD101 − eosinophils, a subtype of eosinophils, could attenuate neutrophil recruitment and accelerate clean-up of neutrophil debris through the production of protectin D1 in lipopolysaccharide (LPS)-induced ARDS murine model. Besides, Krishack et al 12 observed that IL-33–mediated eosinophilia protects against acute lung injury, by reducing neutrophil-associated proinflammatory cytokines and mobilizing tissue repair responses in the bacteria-induced pneumonia model. Eosinophils have been reported to participate in the process of tissue regeneration and repair by producing growth factors.…”

Section: Discussionmentioning

confidence: 99%

Predictive Value of the Baseline and Early Changes in Blood Eosinophils for Short-Term Mortality in Patients with Acute Respiratory Distress Syndrome

Peng¹,

Tang²,

Qi³

et al. 2022

JIR

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Background Eosinophils play an essential role in the pathogenesis of acute respiratory distress syndrome (ARDS). We aimed to assess the association between the baseline blood eosinophils, eosinophil changes during the first week in the intensive care unit (ICU) and short-term patient outcomes. Methods All patients meeting the Berlin definition of ARDS from the Medical Information Mart for Intensive Care IV database were retrospectively analyzed. We used logistic regression, Kaplan–Meier survival and random forest analysis to determine the association between the baseline eosinophils and short-term mortality. Then the trends in eosinophils over time were compared between the survivors and non-survivors using a generalized additive mixed model (GAMM), which is a common approach used for analysis of repeated measurement data. Area under the receiver-operating characteristic curve (AUC) was used to evaluate the predictive value. Results A total of 1685 patients were included, and the 30-day mortality was 25.1%. Kaplan–Meier analysis showed that patients with high baseline eosinophils (>0.3%) had lower 30-day mortality (p < 0.001). Random forest model selected the baseline eosinophils as an important factor associated with 30-day mortality. Multivariable logistic regression analysis identified high baseline eosinophils as an independent factor for 30-day mortality (OR 0.743, 95% CI 0.568–0.970). The GAMM result showed that the levels of eosinophils were increased in both survival and non-survival groups, and the between-group differences increased over time, with an average of 0.154 daily after adjusting for confounders. The AUC of changes in eosinophils within the first week was significantly higher than that of baseline eosinophils. Conclusion There is a negative association between the baseline eosinophils and short-term mortality in ARDS patients, and the differences in eosinophils increased over time between the survivors and non-survivors. Higher increase in eosinophils is associated with decreased short-term mortality, and dynamic monitoring of eosinophils could better predict the survival of ARDS patients.

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“…Eosinophils have been implicated in antibacterial immunity(56), and the increase ratio of eosinophils could help control the bacterial burden in the lung. It has been shown that IL-33 induction of type 2 responses is protective in lethal models of S. aureus sepsis and pneumonia by counterbalancing pro-inflammatory responses(57, 58). While we did not see any differences in IL-33 (data not shown) or gross pathology at 24 hours post infection, we did see a reduction in type 17 cytokines and neutrophils, which has been shown to be protective in patients with S. aureus infection(58, 59).…”

Section: Discussionmentioning

confidence: 99%

Novel Requirement for Staphylococcal Cell Wall-Anchored Protein SasD in Pulmonary Infection

Grousd

Riesmeyer

Cooper

et al. 2022

Preprint

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Staphylococcus aureus can complicate preceding viral infections, including influenza virus. A bacterial infection combined with a preceeding viral infection, known as super-infection, leads to worse outcomes compared to single infection. Most of the super-infection literature focuses on the changes in immune responses to bacteria between homeostatic and virally infected lungs. However, it is unclear how much of an influence bacterial virulence factors have in super-infection. Staphylococcal species express a broad range of cell wall-anchored proteins (CWAs) that have roles in host adhesion, nutrient acquisition, and immune evasion. We screened the importance of these CWAs using mutants lacking individual CWAs in vivo in both bacterial pneumonia and influenza super-infection. In bacterial pneumonia, lacking individual CWAs led to varying decreases in bacterial burden, lung damage, and immune infiltration into the lung. However, the presence of a preceding influenza infection partially abrogated the requirement for CWAs. In the screen, we found that the uncharacterized CWA S. aureus surface protein D (SasD) induced changes in both inflammatory and homeostatic lung markers. We further characterized a SasD mutant (sasD A50.1) in the context of pneumonia. Mice infected with sasD A50.1 had decreased bacterial burden, inflammatory responses, and mortalty compared to wildtype S. aureus. Mice also had reduced levels of IL-1β compared with wildtype, likely derived from macrophages. Reductions in IL-1β transcript levels as well as increased macrophage viability implicate altered macrophage cell death pathways. These data identify a novel virulence factor for S. aureus that influences inflammatory signaling within the lung.

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IL-33–mediated Eosinophilia Protects against Acute Lung Injury

Cited by 23 publications

References 47 publications

Intranasal Immunization With a c-di-GMP-Adjuvanted Acellular Pertussis Vaccine Provides Superior Immunity Against Bordetella pertussis in a Mouse Model

Intranasal Immunization With a c-di-GMP-Adjuvanted Acellular Pertussis Vaccine Provides Superior Immunity Against Bordetella pertussis in a Mouse Model

Predictive Value of the Baseline and Early Changes in Blood Eosinophils for Short-Term Mortality in Patients with Acute Respiratory Distress Syndrome

Novel Requirement for Staphylococcal Cell Wall-Anchored Protein SasD in Pulmonary Infection

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