Biological Sciences and Engineering

Indian Institute of Technology Palakkad&nbsp;(IIT Palakkad or IIT PKD) is a public autonomous&nbsp;engineering&nbsp;and&nbsp;research&nbsp;institute located in&nbsp;Palakkad,&nbsp;Kerala. It was&nbsp;one of the five new&nbsp;IITs&nbsp;proposed in the&nbsp;2014 Union budget of India. The campus was inaugurated on 3 August 2015. The institute has 94 faculty, 978 students, and 63 non-teaching staffs.

IT Palakkad currently offers four-year Bachelor of Technology (B.Tech) and two years MS programmes in 8 different engineering disciplines including&nbsp;Computer Science, Electrical, Mechanical, Civil among others.

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IIT Palakkad

Natural antibodies (nAbs) are most commonly defined as immunoglobulins present in the absence of pathological conditions or deliberate immunizations. Occurrence of nAbs in germ- and antigen-free mice suggest that their production is driven, at least in part, by self-antigens. Accordingly, nAbs are constituted of natural autoantibodies (nAAbs), and can belong to the IgM, IgG, or IgA subclasses. These nAbs provide immediate protection against infection while the adaptive arm of the immune system mounts a specific and long-term response. Beyond immediate protection from infection, nAbs have been shown to play various functional roles in the immune system, which include clearance of apoptotic debris, suppression of autoimmune and inflammatory responses, regulation of B cell responses, selection of the B cell repertoires, and regulation of B cell development. These various functions of nAbs are afforded by their reactivity, which is broad, cross-reactive, and shown to recognize evolutionarily fixed epitopes shared between foreign and self-antigens. Furthermore, nAbs have unique characteristics that also contribute to their functional roles and set them apart from antigen-specific antibodies. In further support for the role of nAbs in the protection against infections and in the maintenance of immune homeostasis, the therapeutic preparation of polyclonal immunoglobulins, intravenous immunoglobulin (IVIG), rich in nAbs is commonly used in the replacement therapy of primary and secondary immunodeficiencies and in the immunotherapy of a large number of autoimmune and inflammatory diseases. Here, we review several topics on nAbs features and functions, and therapeutic applications in human diseases. © 2019, Springer Science+Business Media, LLC, part of Springer Nature.

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Clinical Reviews in Allergy and Immunology

Natural Antibodies: from First-Line Defense Against Pathogens to Perpetual Immune Homeostasis

Cellular and Molecular Immunology

Anti-IgE IgG autoantibodies isolated from therapeutic normal IgG intravenous immunoglobulin induce basophil activation

Basophils are rare granulocytes and dysregulated functions of these cells are associated with several atopic and non-atopic allergic diseases of skin, respiratory system and gastrointestinal tract. Both cytokines and immunoglobulin E (IgE) are implicated in mediating the basophil activation and pathogenesis of these disorders. Several reports have shown that healthy individuals, and patients with allergic disorders display IgG autoantibodies to IgE and hence functional characterization of these anti-IgE IgG autoantibodies is critical. In general, anti-IgE IgG autoantibodies modulate basophil activation irrespective of allergen specificity by interacting with constant domains of IgE. Therefore, an ideal solution to prove the functions of such anti-IgE IgG autoantibodies would be to completely eliminate type I high affinity immunoglobulin E receptor (FcɛRI)-bound IgE from the surface of basophils and to demonstrate in an unequivocal manner the role of anti-IgE IgG autoantibodies. In line with previous reports, our data show that FcɛRI on peripheral blood basophils are almost saturated with IgE. Further, acetic acid buffer (pH 4) efficiently removes these FcɛRI-bound IgE. Although immediately following acetic acid-elution of IgE had no repercussion on the viability of basophils, following 24 hours culture with interleukin-3 (IL-3), the viability and yield of basophils were drastically reduced in acid-treated cells and had repercussion on the induction of activation markers. Lactic acid treatment on the other hand though had no adverse effects on the viability of basophils and IL-3-induced activation, it removed only a small fraction of the cell surface bound IgE. Thus, our results show that acid buffers could be used for the elution of FcɛRI-bound IgE on the basophil surface for the biochemical characterization of IgE antibodies or for the immediate use of basophils to determine their sensitivity to undergo degranulation by specific allergens. However, these methods are not utile for the functional assays of basophils that require longer duration of culture and entire removal of surface IgE to validate the role of anti-IgE IgG autoantibodies that interact with FcɛRI-bound IgE irrespective of allergen specificity. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.

International Journal of Molecular Sciences

Acid stripping of surface IgE antibodies bound to FcεRI is unsuitable for the functional assays that require long-term culture of basophils and entire removal of surface IgE

Frontiers in Cellular and Infection Microbiology

Editorial: The Role of the Fungal Cell Wall in Host-Fungal Interactions

Immune inertness of Aspergillus fumigatus conidia is attributed to its surface rodlet-layer made up of RodAp, characterized by eight conserved cysteine residues forming four disulfide bonds. Earlier, we showed that the conserved cysteine residue point (ccrp) mutations result in conidia devoid of the rodlet layer. Here, we extended our study comparing the surface organization and immunoreactivity of conidia carrying ccrp-mutations with the RODA deletion mutant (∆rodA). Western blot analysis using anti-RodAp antibodies indicated the absence of RodAp in the cytoplasm of ccrp-mutant conidia. Immunolabeling revealed differential reactivity to conidial surface glucans, the ccrp-mutant conidia preferentially binding to α-(1,3)-glucan, ∆rodA conidia selectively bound to β-(1,3)-glucan; the parental strain conidia showed negative labeling. However, permeability of ccrp-mutants and ∆rodA was similar to the parental strain conidia. Proteomic analyses of the conidial surface exposed proteins of the ccrp-mutants showed more similarities with the parental strain, but were significantly different from the ∆rodA. Ccrp-mutant conidia were less immunostimulatory compared to ∆rodA conidia. Our data suggest that (i) the conserved cysteine residues are essential for the trafficking of RodAp and the organization of the rodlet layer on the conidial surface, and (ii) targeted point mutation could be an alternative approach to study the role of fungal cell-wall genes in host–fungal interaction. © MDPI AG. All rights reserved.

Journal of Fungi

The role of roda-conserved cysteine residues in the aspergillus fumigatus conidial surface organization

Autophagy plays an important role in the regulation of autoimmune and autoinflammatory responses of the immune cells. Defective autophagy process is associated with various autoimmune and inflammatory diseases. Moreover, in many of these diseases, the therapeutic use of normal immunoglobulin G or intravenous immunoglobulin (IVIG), a pooled normal IgG preparation, is well documented. Therefore, we explored if IVIG immunotherapy exerts therapeutic benefits via induction of autophagy in the immune cells. Here we show that IVIG induces autophagy in peripheral blood mononuclear cells (PBMCs). Further dissection of this process revealed that IVIG-induced autophagy is restricted to inflammatory cells like monocytes, dendritic cells, and M1 macrophages but not in cells associated with Th2 immune response like M2 macrophages. IVIG induces autophagy by activating AMP-dependent protein kinase, beclin-1, class III phosphoinositide 3-kinase and p38 mitogen-activated protein kinase and by inhibiting mammalian target of rapamycin. Mechanistically, IVIG-induced autophagy is F(ab′)2-dependent but sialylation independent, and requires endocytosis of IgG by innate cells. Inhibition of autophagy compromised the ability of IVIG to suppress the inflammatory cytokines in innate immune cells. Moreover, IVIG therapy in inflammatory myopathies such as dermatomyositis, antisynthetase syndrome and immune-mediated necrotizing myopathy induced autophagy in PBMCs and reduced inflammatory cytokines in the circulation, thus validating the translational importance of these results. Our data provide insight on how circulating normal immunoglobulins maintain immune homeostasis and explain in part the mechanism by which IVIG therapy benefits patients with autoimmune and inflammatory diseases. © 2020, The Author(s).

Cell Death and Disease

Intravenous immunoglobulin mediates anti-inflammatory effects in peripheral blood mononuclear cells by inducing autophagy

Two-dimensional (2D) MXenes have demonstrated outstanding antimicrobial properties owing to their unique physiochemical properties and ultrathin lamellar structure. However, the relationship between MXene sheet size and its antimicrobial activity and how the atomic structure can impact the antibacterial mechanism are yet to be revealed. This study investigates the effect of atomic structure and size dependency on the antibacterial activity of two niobium carbide MXenes (Nb2CTx and Nb4C3Tx) using model Gram-negative and Gram-positive bacteria. The results showed that the bactericidal property of Nb2CTx and Nb4C3Tx against Escherichia coli and Staphylococcus aureus is dependent on the sheet size and atomic structure of both MXenes. 120 $\mu$g/mL delaminated (DL)-Nb2CTx and DL-Nb4C3Tx exhibited growth inhibition of 94.2 and 96.1% for E. coli and 91.6 and 93.7% for S. aureus cells within 3 h of incubation, respectively. The bacterial cell viability decreased with decreasing lateral sheet size of DL-Nb2CTx and DL-Nb4C3Tx down to 160 and 183 nm, respectively. DL-Nb4C3Tx-183 showed higher antibacterial activity than DL-Nb2CTx-160 because of a higher c lattice parameter. Moreover, DL-Nb4C3Tx-183 demonstrated higher oxidative stress on both bacterial cells in comparison with DL-Nb2CTx-160. This study highlights the role of the atomic structure of MXenes and the importance of tailoring the lateral size of the nanosheets to optimize the bactericidal properties of 2D nanomaterials.

ACS Applied Nano Materials

Effect of Sheet Size and Atomic Structure on the Antibacterial Activity of Nb-MXene Nanosheets

The authors wish to make the following corrections to this paper [1]: Two dot-plots in the Panel E of Figure 1 (labeled under VAP and VAA) have been inadvertently duplicated during the final preparation of figures. We would like to change the Panel E of Figure 1 in paper [1] to the correct version. © 2019 by the authors.

Molecules

Erratum: Differential Effects of Viscum album Preparations on the Maturation and Activation of Human Dendritic Cells and CD4+ T Cell Responses (Molecules (2016) 21(912) DOI: 10.3390/molecules21070912)

The rodlet structure present on the Aspergillus fumigatus conidial surface hides conidia from immune recognition. In spite of the essential biological role of the rodlets, the molecular basis for their self-assembly and disaggregation is not known. Analysis of the soluble forms of conidia-extracted and recombinant RodA by NMR spectroscopy has indicated the importance of disulfide bonds and identified two dynamic regions as likely candidates for conformational change and intermolecular interactions during conversion of RodA into the amyloid rodlet structure. Point mutations introduced into the RODA sequence confirmed that (1)mutation of a single cysteine was sufficient to block rodlet formation on the conidial surface and (2)both presumed amyloidogenic regions were needed for proper rodlet assembly. Mutations in the two putative amyloidogenic regions retarded and disturbed, but did not completely inhibit, the formation of the rodlets in vitro and on the conidial surface. Even in a disturbed form, the presence of rodlets on the surface of the conidia was sufficient to immunosilence the conidium. However, in contrast to the parental conidia, long exposure of mutant conidia lacking disulfide bridges within RodA or expressing RodA carrying the double (I115S/I146G)mutation activated dendritic cells with the subsequent secretion of proinflammatory cytokines. The immune reactivity of the RodA mutant conidia was not due to a modification in the RodA structure, but to the exposure of different pathogen-associated molecular patterns on the surface as a result of the modification of the rodlet surface layer. The full degradation of the rodlet layer, which occurs during early germination, is due to a complex array of cell wall bound proteases. As reported earlier, this loss of the rodlet layer lead to a strong anti-fumigatus host immune response in mouse lungs. © 2019 The Authors

Cell Surface

Assembly and disassembly of Aspergillus fumigatus conidial rodlets

The discovery of two-dimensional (2D) transition metal carbides and nitrides (MXenes) in 2011 has expanded the pool of nanomaterials available for a variety of applications. Characteristic properties of MXenes, such as high conductivity, hydrophilicity and catalytic activity have led to a growing research interest for their use in environmental remediation and water treatment applications. This review summarizes recent advances in the synthesis and applications of MXenes as adsorbents, desalination membranes, electrodes for electrochemical deionization and catalytic or antibacterial agents for water purification and other environmental remediation processes. The overview also features discussions on the computational attempts, biocompatibility and environmental impact in the exploration of MXenes for water applications, highlighting the challenges and opportunities of these advanced 2D materials.