Humoral Immune Responses to Amebic Liver Abscess

Background: Amebic liver abscess (ALA) is an ancient parasitic disease caused by E. histolytica described first by Hippocrates. It is endemic worldwide, mainly in tropic and subtropics countries. About 50 million true E. histolytica infections and approximately 100,000 deaths occur each year globally. In Bangladesh, exact incidences of amebic liver abscess cases are not estimated, but hospital reports indicate that it is endemic. Immunity and immune responses in acute and post infections of ALA are not well understood to date. However, the understanding of immunology is essential to know disease progression, recovery, morbidity, and mortality as well as diagnosis and newer prevention strategies like vaccine development. In this 15-month prospective and follow-up study, different antibody responses are estimated periodically. Methods: About 90 amebic liver abscess patients diagnosed initially by ultra-sonogram confirmed followed by Real-Time PCR were selected for this study. All were admitted into Rajshahi Medical College Hospital, Bangladesh. Antibody responses against different antigens, which include Serum anti-lectin IgG, Salivary anti-CRD (carbohydrate recognition domain) Ig A, and Stool anti-CRD (carbohydrate recognition domain) IgA were estimated by ELISA periodically thrice, in acute stage after 06 and 09 months and between 12 and 15 months. Results: Serum anti-lectin IgG in ALA persists remarkably high well up to 09 months in 98% cases, Secretory anti-CRD IgA was also determined from the saliva, and only 36(40%) show positive titer during first 06 months, and about 40% of ALA cases show high titer of anti-CRD IgA from stool samples in first six months of infection. Conclusion: Only serum anti lectin Ig G showed significant high titer in 98% of cases in the acute stage and up to nine months of infection. TAJ 2021; 34: No-1: 05-08

Blood Levels of Galectin-9, an Immuno-Regulating Molecule, Reflects the Severity for the Acute and Chronic Infectious Diseases

Galectin-9 (Gal-9) is a β-galactoside-binding lectin capable of promoting or suppressing the progression of infectious diseases. This protein is susceptible to cleavage of its linker-peptides by several proteases, and the resulting cleaved forms, N-terminal carbohydrate recognition domain (CRD) and C-terminal CRD, bind to various glycans. It has been suggested that full-length (FL)-Gal-9 and the truncated (Tr)-Gal-9s could exert different functions from one another via their different glycan-binding activities. We propose that FL-Gal-9 regulates the pathogenesis of infectious diseases, including human immunodeficiency virus (HIV) infection, HIV co-infected with opportunistic infection (HIV/OI), dengue, malaria, leptospirosis, and tuberculosis (TB). We also suggest that the blood levels of FL-Gal-9 reflect the severity of dengue, malaria, and HIV/OI, and those of Tr-Gal-9 markedly reflect the severity of HIV/OI. Recently, matrix metallopeptidase-9 (MMP-9) was suggested to be an indicator of respiratory failure from coronavirus disease 2019 (COVID-19) as well as useful for differentiating pulmonary from extrapulmonary TB. The protease cleavage of FL-Gal-9 may lead to uncontrolled hyper-immune activation, including a cytokine storm. In summary, Gal-9 has potential to reflect the disease severity for the acute and chronic infectious diseases.

Cholesteryl glucosides signal through the carbohydrate recognition domain of the macrophage inducible C-type lectin (mincle)

H. pylori derived cholesteryl glycosides signal through the Carbohydrate Recognition Domain (CRD) of the Macrophage inducible C-type lectin (Mincle).

TETRALEC, Artificial Tetrameric Lectins: A Tool to Screen Ligand and Pathogen Interactions

C-type lectin receptor (CLR)/carbohydrate recognition occurs through low affinity interactions. Nature compensates that weakness by multivalent display of the lectin carbohydrate recognition domain (CRD) at the cell surface. Mimicking these low affinity interactions in vitro is essential to better understand CLR/glycan interactions. Here, we present a strategy to create a generic construct with a tetrameric presentation of the CRD for any CLR, termed TETRALEC. We applied our strategy to a naturally occurring tetrameric CRD, DC-SIGNR, and compared the TETRALEC ligand binding capacity by synthetic N- and O-glycans microarray using three different DC-SIGNR constructs i) its natural tetrameric counterpart, ii) the monomeric CRD and iii) a dimeric Fc-CRD fusion. DC-SIGNR TETRALEC construct showed a similar binding profile to that of its natural tetrameric counterpart. However, differences observed in recognition of low affinity ligands underlined the importance of the CRD spatial arrangement. Moreover, we further extended the applications of DC-SIGNR TETRALEC to evaluate CLR/pathogens interactions. This construct was able to recognize heat-killed Candida albicans by flow cytometry and confocal microscopy, a so far unreported specificity of DC-SIGNR. In summary, the newly developed DC-SIGNR TETRALEC tool proved to be useful to unravel novel CLR/glycan interactions, an approach which could be applied to other CLRs.

Galectins and Ovarian Cancer

Ovarian cancer is known for its aggressive pathological features, including the capacity to undergo epithelial to mesenchymal transition, promoting angiogenesis, metastatic potential, chemoresistance, inhibiting apoptosis, immunosuppression and promoting stem-like features. Galectins, a family of glycan-binding proteins defined by a conserved carbohydrate recognition domain, can modulate many of these processes, enabling them to contribute to the pathology of ovarian cancer. Our goal herein was to review specific galectin members identified in the context of ovarian cancer, with emphasis on their association with clinical and pathological features, implied functions, diagnostic or prognostic potential and strategies being developed to disrupt their negative actions.

Pivotal role of the carbohydrate recognition domain in self-interaction of CLEC4A to elicit the ITIM-mediated inhibitory function in murine conventional dendritic cells in vitro

C-type lectin receptors (CLRs), pattern recognition receptors (PRRs) with a characteristic carbohydrate recognition domain (CRD) in the extracellular portion, mediate crucial cellular functions upon recognition of glycosylated pathogens and self-glycoproteins. CLEC4A is the only classical CLR that possesses an intracellular immunoreceptor tyrosine-based inhibitory motif (ITIM), which possibly transduces negative signals. However, how CLEC4A exerts cellular inhibition remains unclear. Here, we report that the self-interaction of CLEC4A through the CRD is required for the ITIM-mediated suppressive function in conventional dendritic cells (cDCs). Human type 2 cDCs (cDC2) and monocytes display a higher expression of CLEC4A than cDC1 and plasmacytoid DCs (pDCs) as well as B cells. The extracellular portion of CLEC4A specifically binds to a murine cDC cell line expressing CLEC4A, while its extracellular portion lacking the N-glycosylation site or the EPS motif within the CRD reduces their association. Furthermore, the deletion of the EPS motif within the CRD or ITIM in CLEC4A almost completely impairs its suppressive effect on the activation of the murine cDC cell line, whereas the absence of the N-glycosylation site within the CRD exhibits partial inhibition on their activation. On the other hand, antagonistic monoclonal antibody (mAb) to CLEC4A, which inhibits the self-interaction of CLEC4A and its downstream signaling in murine transfectants, enhances the activation of monocytes and monocyte-derived immature DCs upon stimulation with a Toll-like receptor (TLR) ligand. Thus, our findings suggest a pivotal role of the CRD in self-interaction of CLEC4A to elicit the ITIM-mediated inhibitory signal for the control of the function of cDCs.