The Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), accountable for Coronavirus disease 2019 (COVID-19), may cause hyperglycemia and additional systemic complexity in metabolic ...parameters. It is unsure even if the virus itself causes type 1 or type 2 diabetes mellitus (T1DM or T2DM). Furthermore, it is still unclear whether even recuperating COVID-19 individuals have an increased chance to develop new-onset diabetes.
We wanted to determine the impact of COVID-19 on the levels of adipokines, pancreatic hormones, incretins and cytokines in acute COVID-19, convalescent COVID-19 and control children through an observational study. We performed a multiplex immune assay analysis and compared the plasma levels of adipocytokines, pancreatic hormones, incretins and cytokines of children presenting with acute COVID-19 infection and convalescent COVID-19.
Acute COVID-19 children had significantly elevated levels of adipsin, leptin, insulin, C-peptide, glucagon and ghrelin in comparison to convalescent COVID-19 and controls. Similarly, convalescent COVID-19 children had elevated levels of adipsin, leptin, insulin, C-peptide, glucagon, ghrelin and Glucagon-like peptide-1 (GLP-1) in comparison to control children. On the other hand, acute COVID-19 children had significantly decreased levels of adiponectin and Gastric Inhibitory Peptide (GIP) in comparison to convalescent COVID-19 and controls. Similarly, convalescent COVID-19 children had decreased levels of adiponectin and GIP in comparison to control children. Acute COVID-19 children had significantly elevated levels of cytokines, (Interferon (IFN)) IFNγ, Interleukins (IL)-2, TNFα, IL-1α, IL-1β, IFNα, IFNβ, IL-6, IL-12, IL-17A and Granulocyte-Colony Stimulating Factors (G-CSF) in comparison to convalescent COVID-19 and controls. Convalescent COVID-19 children had elevated levels of IFNγ, IL-2, TNFα, IL-1α, IL-1β, IFNα, IFNβ, IL-6, IL-12, IL-17A and G-CSF in comparison to control children. Additionally, Principal component Analysis (PCA) analysis distinguishes acute COVID-19 from convalescent COVID-19 and controls. The adipokines exhibited a significant correlation with the levels of pro-inflammatory cytokines.
Children with acute COVID-19 show significant glycometabolic impairment and exaggerated cytokine responses, which is different from convalescent COVID-19 infection and controls.
Despite marked improvement in the quality of lives across the globe, more than 2 million individuals in socioeconomically disadvantaged environments remain infected by helminth (worm) parasites. ...Owing to the longevity of the worms and paucity of immunologic controls, these parasites survive for long periods within the bloodstream, lymphatics, and gastrointestinal tract resulting in pathologic conditions such as anemia, cirrhosis, and lymphatic filariasis. Despite infection, an asymptomatic state may be maintained by the host immunoregulatory environment, which involves multiple levels of regulatory cells and cytokines; a breakdown of this regulation is observed in pathological disease. The role of TLR expression and function in relation to intracellular parasites has been documented but limited studies are available for multicellular helminth parasites. In this review, we discuss the unique and shared host effector mechanisms elicited by systemic helminth parasites and their derived products, including the role of TLRs and sphingolipids. Understanding and exploiting the interactions between these parasites and the host regulatory network are likely to highlight new strategies to control both infectious and immunological diseases.
Tissue invasive helminth infections and tuberculosis (TB) are co-endemic in many parts of the world and can trigger immune responses that might antagonize each other. We have previously shown that ...helminth infections modulate the Th1 and Th17 responses to mycobacterial-antigens in latent TB. To determine whether helminth infections modulate antigen-specific and non-specific immune responses in active pulmonary TB, we examined CD4(+) and CD8(+) T cell responses as well as the systemic (plasma) cytokine levels in individuals with pulmonary TB with or without two distinct helminth infections-Wuchereria bancrofti and Strongyloides stercoralis infection. By analyzing the frequencies of Th1 and Th17 CD4(+) and CD8(+) T cells and their component subsets (including multifunctional cells), we report a significant diminution in the mycobacterial-specific frequencies of mono- and multi-functional CD4(+) Th1 and (to a lesser extent) Th17 cells when concomitant filarial or Strongyloides infection occurs. The impairment in CD4(+) and CD8(+) T cell cytokine responses was antigen-specific as polyclonal activated T cell frequencies were equivalent irrespective of helminth infection status. This diminution in T cell responses was also reflected in diminished circulating levels of Th1 (IFN-γ, TNF-α and IL-2)- and Th17 (IL-17A and IL-17F)-associated cytokines. Finally, we demonstrate that for the filarial co-infections at least, this diminished frequency of multifunctional CD4(+) T cell responses was partially dependent on IL-10 as IL-10 blockade significantly increased the frequencies of CD4(+) Th1 cells. Thus, co-existent helminth infection is associated with an IL-10 mediated (for filarial infection) profound inhibition of antigen-specific CD4(+) T cell responses as well as protective systemic cytokine responses in active pulmonary TB.
Helminth infections are known to influence T cell responses in latent tuberculosis (LTBI). Whether helminth infections also modulate B cell responses in helminth-tuberculosis co-infection is not ...known.
We assessed Mycobacterium tuberculosis (Mtb)-antigen specific IgM and IgG levels, circulating levels of the B cell growth factors, BAFF and APRIL and the absolute numbers of the various B cell subsets in individuals with LTBI, LTBI with coincident Strongyloides stercoralis (Ss) infection (LTBI/Ss) and in those with Ss infection alone (Ss). We also measured the above-mentioned parameters in the LTBI-Ss group after anthelmintic therapy.
Our data reveal that LTBI-Ss exhibit significantly diminished levels of Mtb-specific IgM and IgG, BAFF and APRIL levels in comparison to those with LTBI. Similarly, those with LTBI-Ss had significantly diminished numbers of all B cell subsets (naïve, immature, classical memory, activated memory, atypical memory and plasma cells) compared to those with LTBI. There was a positive correlation between Mtb-antigen specific IgM and IgG levels and BAFF and APRIL levels that were in turn related to the numbers of activated memory B cells, atypical memory B cells and plasma cells. Finally, anthelmintic treatment resulted in significantly increased levels of Mtb-antigen specific IgM and IgG levels and the numbers of each of the B cell subsets.
Our data, therefore, reveal that Ss infection is associated with significant modulation of Mtb-specific antibody responses, the levels of B cell growth factors and the numbers of B cells (and their component subsets).
Type 2 diabetes mellitus (T2DM) is characterized by heightened systemic inflammation and microbial translocation. Whether concomitant helminth infections can modulate this systemic response is ...unclear. We examined the presence of markers of systemic inflammation (levels of acute phase proteins) and of microbial translocation levels of lipopolysaccharide (LPS) and its associated products in T2DM individuals with (
) or without (
)
(
) infection. We also analyzed these parameters at 6 months following anthelmintic treatment in
individuals.
individuals exhibited significantly diminished levels of alpha-2 macroglobulin, C-reactive protein, haptoglobin and serum amyloid protein A1 compared to
individuals and these levels increased significantly following therapy. Similarly,
individuals exhibited significantly diminished levels of LPS, sCD14, intestinal fatty acid binding protein, LPS binding protein and endotoxin IgG antibody and most of these levels increased significantly following therapy. Thus, helminth infection is associated with attenuation of systemic inflammation and microbial translocation in T2DM and its reversal following anthelmintic therapy.
Plasmacytoid and myeloid dendritic cells play a vital role in the protection against viral infections. In COVID-19, there is an impairment of dendritic cell (DC) function and interferon secretion ...which has been correlated with disease severity.
In this study, we described the frequency of DC subsets and the plasma levels of Type I (IFNα, IFNβ) and Type III Interferons (IFNλ1), IFNλ2) and IFNλ3) in seven groups of COVID-19 individuals, classified based on days since RT-PCR confirmation of SARS-CoV2 infection. Our data shows that the frequencies of pDC and mDC increase from Days 15-30 to Days 61-90 and plateau thereafter. Similarly, the levels of IFNα, IFNβ, IFNλ1, IFNλ2 and IFNλ3 increase from Days 15-30 to Days 61-90 and plateau thereafter. COVID-19 patients with severe disease exhibit diminished frequencies of pDC and mDC and decreased levels of IFNα, IFNβ, IFNλ1, IFNλ2 and IFNλ3. Finally, the percentages of DC subsets positively correlated with the levels of Type I and Type III IFNs.
Thus, our study provides evidence of restoration of homeostatic levels in DC subset frequencies and circulating levels of Type I and Type III IFNs in convalescent COVID-19 individuals.
CD4+ and CD8+ T cells are central players in immunity to helminth infections. However, the role of T cell subsets in human helminth infections is not well understood. In addition, the common γc ...cytokines, IL-2, IL-4, IL-7, IL-9 and IL-15 play an important role in the maintenance of these CD4+ and CD8+ T cell subsets.
To examine the major T cell subsets and their association with the common γc cytokines, the absolute numbers of CD4+ and CD8+ naïve, central memory, effector memory and effector cells and the plasma levels of IL-2, IL-4, IL-7, IL-9 and IL-15 were measured in Strongyloides stercoralis (Ss) infected (INF, n = 60), helminth-uninfected (UN, n = 58) and in post treatment INF individuals.
Ss infection is characterized by significantly increased absolute numbers of naïve and decreased absolute numbers of central and effector memory CD4+ T cells in comparison to UN individuals. No significant difference in the numbers of CD8+ T cell subsets was observed between the groups. The numbers of naïve cells and central memory CD4+ T cells were significantly reversed after anthelmintic treatment. Circulating levels of IL-2, IL-7 and IL-15 were significantly diminished, whereas the levels of IL-4 and IL-9 were significantly increased in INF compared to UN individuals. Following anthelminthic treatment, IL-2, IL-7 and IL-15 levels were significantly increased, while IL-4 and IL-9 levels were significantly decreased. Our data also showed a significant positive correlation between the levels of IL-7 and the numbers of central and effector memory CD4+ T cells.
Ss infection is characterized by alterations in the absolute numbers of CD4+ T cell subsets and altered levels of common γc cytokines IL-2, IL-4, IL-7, IL-9 and IL-15; alterations which are partially reversed after anthelmintic treatment.
Type III IFNs are important players in immunity to viral and bacterial infections. However, their association with helminth infections has not been examined. To explore the association of Type III ...IFNs with
(
) infection, we examined the systemic levels of IFN lambda-1, IFN lambda-2 and IFN lambda-3, IL-10, and CXCL10/IP-10 in
infected (INF,
= 44), helminth-uninfected (UN,
= 44) and in post-treatment INF individuals. We also examined the levels of IFN lambda-1, IFN lambda-2 and IFN lambda-3, IL-10, and CXCL10/IP-10 in whole blood culture supernatants stimulated with
somatic antigens, or PPD or LPS. Finally, we performed correlations of systemic Type III IFN levels with absolute numbers of dendritic cell subsets.
infection is characterized by elevated systemic levels of IFN lambda-1, IFN lambda-2 and IFN lambda-3, IL-10, and CXCL10/IP-10 in comparison to UN individuals and a significant reduction following anthelmintic treatment.
infection is also characterized by elevated levels of unstimulated or
antigen stimulated levels of IFN lambda-1, IFN lambda-2 and IFN lambda-3, CXCL10/IP-10 and a significant reduction following treatment. In addition,
infection is characterized by increased numbers of plasmacytoid and myeloid dendritic cells in comparison to UN individuals, with a significant reduction following anthelmintic treatment of INF individuals. Finally,
infection exhibits a significant positive correlation between the systemic levels of IFN lambda-2 and IFN lambda-3 and the numbers of plasmacytoid dendritic cells. Thus,
infection is characterized by elevations in systemic and antigen-induced levels of Type III IFNs, which is positively associated with the numbers of plasmacytoid dendritic cells and reversed upon anthelmintic treatment.
Background
Severe Acute Respiratory Syndrome Coronavirus‐2 (SARS‐CoV‐2), a causative pathogen of the COVID‐19 pandemic, affects all age groups. However, various studies have shown that COVID‐19 ...presentation and severity vary considerably with age. We, therefore, wanted to examine the differences between the immune responses of children with COVID‐19 and elderly COVID‐19 individuals.
Methods
We analyzed cytokines, chemokines, growth factors, and acute phase proteins in acute and convalescent COVID‐19 children and the elderly with acute and convalescent COVID‐19.
Results
We show that most of the pro‐inflammatory cytokines (interferon IFNγ, interleukin IL‐2, tumor necrosis factor‐α TNFα, IL‐1α, IFNα, IFNβ, IL‐6, IL‐12, IL‐3, IL‐7, IL‐1Ra, IL‐13, and IL‐10), chemokines (CCL4, CCL11, CCL19, CXCL1, CXCL2, CXCL8, and CXL10), growth factors (vascular endothelial growth factor and CD40L) and acute phase proteins (C‐reactive protein, serum amyloid P, and haptoglobin) were decreased in children with acute COVID 19 as compared with elderly individuals. In contrast, children with acute COVID‐19 exhibited elevated levels of cytokines‐ IL‐1β, IL‐33, IL‐4, IL‐5, and IL‐25, growth factors—fibroblast growth factor‐2, platelet‐ derived growth factors‐BB, and transforming growth factorα as compared with elderly individuals. Similar, differences were manifest in children and elderly with convalescent COVID‐19.
Conclusion
Thus, COVID‐19 children are characterized by distinct cytokine/chemokine/growth factor/acute phase protein markers that are markedly different from elderly COVID‐19 individuals.
Children with COVID‐19 are characterized by distinct cytokine/chemokine/growth factor/acute phase protein markers that are markedly different from elderly COVID‐19 individuals. CRP, C‐reactive protein; IFN, interferon; IL, interleukin; PCA, principal component analysis; TGFα, transforming growth factorα; TNFα, tumor necrosis factorα.
Microbial translocation (MT) is the process by which microbes or microbial products translocate from the intestine to the systemic circulation. MT is a common cause of systemic immune activation in ...HIV infection and is associated with reduced frequencies of CD4(+) T cells; no data exist, however, on the role of MT in intestinal helminth infections.
We measured the plasma levels of MT markers, acute-phase proteins, and pro- and anti-inflammatory cytokines in individuals with or without hookworm infections. We also estimated the absolute counts of CD4(+) and CD8(+) T cells as well as the frequencies of memory T cell and dendritic cell subsets. Finally, we also measured the levels of all of these parameters in a subset of individuals following treatment of hookworm infection.
Our data suggest that hookworm infection is characterized by increased levels of markers associated with MT but not acute-phase proteins nor pro-inflammatory cytokines. Hookworm infections were also associated with increased levels of the anti-inflammatory cytokine--IL-10, which was positively correlated with levels of lipopolysaccharide (LPS). In addition, MT was associated with decreased numbers of CD8(+) T cells and diminished frequencies of particular dendritic cell subsets. Antihelmintic treatment of hookworm infection resulted in reversal of some of the hematologic and microbiologic alterations.
Our data provide compelling evidence for MT in a human intestinal helminth infection and its association with perturbations in the T cell and antigen-presenting cell compartments of the immune system. Our data also reveal that at least one dominant counter-regulatory mechanism i.e. increased IL-10 production might potentially protect against systemic immune activation in hookworm infections.
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