SARS‐CoV2 pneumonia recovery is linked to expansion of innate lymphoid cells type 2 expressing CCR10

Gomes, André M. C.; Farias, Guilherme B.; Dias‐Silva, Manuel; Laia, Joel; Trombetta, Amelia Chiara; Godinho‐Santos, Ana; Rosmaninho, Pedro; Santos, Diana; Conceição, Carolina M.; Costa‐Reis, Renato; Adão‐Serrano, Maria; Mota, Catarina; Almeida, Afonso R. M.; Sousa, Ana E.; Fernandes, S.

doi:10.1002/eji.202149311

Cited by 16 publications

(13 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Preliminary clinical studies have shown that worsened disease severity and increased risk of hospitalization are associated with reductions in ILC abundance 178 and that expansion of the ILC2 population is linked to recovery from COVID-19 (ref. 179 ), highlighting the importance of innate immune cells to counteract infection 180 . The innate immune system uses an array of sensors and effector molecules, including TLRs, RLRs, NLRs and inflammasome sensors as well as cGAS and STING, to directly and indirectly sense the virus or viral components.…”

Section: Summary and Future Directionsmentioning

confidence: 99%

Innate immunity: the first line of defense against SARS-CoV-2

2022

View full text Add to dashboard Cite

In 2019, SARS-CoV-2 emerged as a new pathogen that resulted in the COVID-19 pandemic. Initially identified in Wuhan, China in December 2019 (refs. 1,2 ), SARS-CoV-2 rapidly spread throughout the world, leading to an ongoing public health crisis, and, as of 2 December 2021, there have been over 263 million infections and 5.2 million deaths 3 . SARS-CoV-2 causes upper and lower respiratory tract infections that are often associated with fever, cough and loss of smell and taste. Most infections remain mild, and up to 20-40% of patients are asymptomatic. However, some patients experience more severe disease and develop systemic inflammation, tissue damage, acute respiratory distress syndrome, thromboembolic complications, cardiac injury and/or cytokine storm, which can be fatal 1,4 (Fig. 1). The risk of COVID-19 disease severity depends on comorbidities (for example, diabetes, hypertension and obesity), age, ethnicity, genetic factors, vaccination status and other conditions 5 , making understanding the underlying disease mechanisms important for risk stratification and clinical triage.

show abstract

Section: Summary and Future Directionsmentioning

confidence: 99%

Innate immunity: the first line of defense against SARS-CoV-2

2022

View full text Add to dashboard Cite

show abstract

“…ILCp decreased in COVID-19 patients but without significance, while the absolute number of ILC type-3 (Lin CD127+CD117+CD294-) increased compared to Severe patients [59]. However, individuals recovering had a 2.39-fold increase in ILC abundance as compared to time of acute disease [56] and had an expansion of CCR10 expressing ILC2 [58] as well.…”

Section: Ilcmentioning

confidence: 94%

“…We gathered 4 papers discussing the involvement of ILC and their subsets (ILC1, ILC2, ILCp [55][56][57][58] and ILC3 [59] in COVID-19 patients with severe or moderate symptoms. Only one study considered as control non-COVID-19 patients and evaluated recovered patients; the other ones used as controls only the Healthy subjects (Table 4).…”

Section: Ilcmentioning

confidence: 99%

“…The study on recovery patients is an attractive topic that we want to highlight, given the possible consequences of the virus infection on the patients. Indeed, only for MAIT, NKT, and ILC (particularly ILC2 subtype [58]), individuals recovering from COVID-19 restored frequency and absolute number as compared to the time of acute disease. Additionally, discharged patients show higher levels of CD69 compared to those who remained in critical care.…”

Section: Remarkable Considerations and Conclusionmentioning

confidence: 99%

See 1 more Smart Citation

Comprehensive Analysis of the ILCs and Unconventional T Cells in Virus Infection: Profiling and Dynamics Associated with COVID-19 Disease for a Future Monitoring System and Therapeutic Opportunities

Presti

Gaetano

Pioggia

et al. 2022

Cells

View full text Add to dashboard Cite

This review is a comprehensive analysis of the effects of SARS-CoV-2 infection on Unconventional T cells and innate lymphoid cells (ILCs). COVID-19 affected patients show dysregulation of their adaptive immune systems, but many questions remain unsolved on the behavior of Unconventional cells and ILCs during infection, considering their role in maintaining homeostasis in tissue. Therefore, we highlight the differences that exist among the studies in cohorts of patients who in general were categorized considering symptoms and hospitalization. Moreover, we make a critical analysis of the presence of particular clusters of cells that express activation and exhausted markers for each group in order to bring out potential diagnostic factors unconsidered before now. We also focus our attention on studies that take into consideration recovered patients. Indeed, it could be useful to determine Unconventional T cells’ and ILCs’ frequencies and functions in longitudinal studies because it could represent a way to monitor the immune status of SARS-CoV-2-infected subjects. Possible changes in cell frequencies or activation profiles could be potentially useful as prognostic biomarkers and for future therapy. Currently, there are no efficacious therapies for SARS-CoV-2 infection, but deep studies on involvement of Unconventional T cells and ILCs in the pathogenesis of COVID-19 could be promising for targeted therapies.

show abstract

“…22 Total peripheral ILC levels were also found to be decreased in SARS-CoV-2-infected coronavirus disease-19 (COVID-19) patients, with ILC2 decreased in severe but not in moderate patients. 23–25 Moreover, in infants with respiratory syncytial virus bronchiolitis, elevated levels of ILC2 in the airways were found to associate with disease severity. 26 Overall, these studies show an effect of viral infections on the ILC landscape.…”

Section: Introductionmentioning

confidence: 99%

Innate lymphoid cells are activated and their levels correlate with viral load in patients with Puumala hantavirus caused hemorrhagic fever with renal syndrome

García

Tauriainen

et al. 2022

Preprint

View full text Add to dashboard Cite

BackgroundInnate lymphoid cells (ILCs) are involved in immunity and homeostasis but, except for natural killer (NK) cells, their role in human viral infections is not well known. Puumala virus (PUUV) is a hantavirus that causes the acute zoonotic disease hemorrhagic fever with renal syndrome (HFRS). HFRS is characterized by strong systemic inflammation and NK cells are highly activated in HFRS, suggesting that also other ILCs might be responding to infection.MethodsHere we phenotypically analyzed peripheral ILCs in acute and convalescent PUUV-infected HFRS patients. Additionally, plasma levels of soluble factors and viral load were analyzed.FindingsOverall, the frequencies of NK cells and naïve ILCs were reduced while the frequency of ILC2, in particular the ILC2-lineage committed c-Kitlo ILC2 subset, was increased during acute HFRS. Interestingly, we observed a negative correlation between viral load and frequencies of both NK and non-NK ILCs in acute HFRS. Phenotypically, ILCs displayed an activated profile with increased proliferation, and showed altered expression of several homing markers during acute HFRS. In line with the observation of activated ILCs, plasma levels of inflammatory proteins, including the ILC-associated cytokines interleukin (IL)-13, IL-23, IL-25, IL-33, and thymic stromal lymphopoietin (TSLP), were elevated during acute HFRS.InterpretationThese findings indicate a general involvement of ILCs in response to human hantavirus infection. Further, this constitutes the first comprehensive study of ILCs in a hantavirus-caused disease, aiding in further understanding the role of these cells in disease pathogenesis and in human viral infections in general.FundingA full list of funding bodies that contributed to this study can be found in the Acknowledgements section.RESEARCH IN CONTEXTEvidence before this studyInnate lymphoid cells (ILCs) include a broad range of innate cell subsets involved, among other functions, in early response to infections. Natural killer (NK) cells have been broadly characterized in human viral infections, but much less is known in such context about other more recently discovered ILCs. Puumala virus is one of the causative agents of hemorrhagic fever with renal syndrome (HFRS), an acute zoonotic disease characterized by systemic inflammation. No current treatment or vaccines are available to date for hantavirus-caused diseases and pathogenesis is still not fully understood. A PubMed search up until April 2022 using a combination of the terms virus, Puumala virus, hantavirus, HFRS, ILCs, and NK cells shows that while studies have been performed characterizing NK cells in HFRS, no studies are available on the rest of ILCs in hantavirus-caused diseases, which in addition have been studied in only a handful of human viral infections.Added value of this studyIn this study we thoroughly characterized the ILC landscape in circulation and its milieu in acute and convalescent Puumala-infected HFRS patients. We found that the frequency of NK cells and other ILC subsets was altered in the acute HFRS patients as compared to convalescent HFRS patients and control individuals, with a decrease in NK cells and naïve ILCs, and an increase in ILC2. In particular the ILC2-lineage committed c-Kitlo ILC2 subset was found increased. Total ILCs showed increased levels of activation and proliferation, and signs of altered migration patterns in acute HFRS patients. The finding of elevated levels of several soluble inflammatory proteins associated with ILCs in acute HFRS patients further suggests an implication of ILCs in HFRS. Moreover, an association between the frequency of NK cells and non-NK ILCs and plasma viral load suggest a possible connection between viremia and the activity of these cell types during the course of disease.Implications of all the available evidenceOur research shows that all circulating ILCs, including non-NK ILCs, are activated, proliferating, and correlate with viral load in acute HFRS patients, indicating a general involvement in human hantavirus infection and disease. Being the first comprehensive study on ILCs in hantavirus infections, further research will give relevant insight into the roles of ILCs in disease pathogenesis and protection.

show abstract

SARS‐CoV2 pneumonia recovery is linked to expansion of innate lymphoid cells type 2 expressing CCR10

Cited by 16 publications

References 33 publications

Innate immunity: the first line of defense against SARS-CoV-2

Innate immunity: the first line of defense against SARS-CoV-2

Comprehensive Analysis of the ILCs and Unconventional T Cells in Virus Infection: Profiling and Dynamics Associated with COVID-19 Disease for a Future Monitoring System and Therapeutic Opportunities

Innate lymphoid cells are activated and their levels correlate with viral load in patients with Puumala hantavirus caused hemorrhagic fever with renal syndrome

Contact Info

Product

Resources

About