Fungi, usually present as commensals, are a major cause of opportunistic infections in immunocompromised patients. Such infections, if not diagnosed or treated properly, can prove fatal. However, in most cases healthy individuals are able to avert the fungal attacks by mounting proper antifungal immune responses. Among the pattern recognition receptors (PRRs), C-type lectin receptors (CLRs) are the major players in antifungal immunity. CLRs can recognize carbohydrate ligands, such as β-glucans and mannans, which are mainly found on fungal cell surfaces. They induce proinflammatory immune reactions, including phagocytosis, oxidative burst, cytokine, and chemokine production from innate effector cells, as well as activation of adaptive immunity via Th17 responses. CLRs such as Dectin-1, Dectin-2, Mincle, mannose receptor (MR), and DC-SIGN can recognize many disease-causing fungi and also collaborate with each other as well as other PRRs in mounting a fungi-specific immune response. Mutations in these receptors affect the host response and have been linked to a higher risk in contracting fungal infections. This review focuses on how CLRs on various immune cells orchestrate the antifungal response and on the contribution of single nucleotide polymorphisms in these receptors toward the risk of developing such infections.
Mycobacterium tuberculosis (Mtb), the etiologic agent of tuberculosis (TB), is recognized by a number of pathogen recognition receptors (PRRs), either soluble or predominantly expressed on the surface of various cells of innate and adaptive immunity. C-type lectin receptors (CTLRs) are a class of PRRs which can recognize a variety of endogenous and exogenous ligands, thereby playing a crucial role in immunity, as well as in maintaining homeostasis. Mtb surface ligands, including mannose-capped lipoarabinomannan and cord factor, are important immune modulators which recently have been found to be directly recognized by several CTLRs. Receptor ligation is followed by cellular activation, mainly via nuclear factor κB mediated by a series of adaptors with subsequent expression of pro-inflammatory cytokines. Mtb recognition by CTLRs and their cross talk with other PRRs on immune cells is of key importance for the better understanding of the Mtb-induced complexity of the host immune responses. Epidemiological studies have shown that single nucleotide polymorphisms (SNPs) in several PRRs, as well as the adaptors in their signaling cascades, are directly involved in the susceptibility for developing disease and the disease outcome. In addition, an increasing number of CTLRs have been studied for their functional effects in the pathogenesis of TB. This review summarizes current knowledge regarding the various roles played by different CTLRs in TB, as well as the role of their SNPs associated with disease susceptibility and outcome in different human populations.
BackgroundExisting reading schemes for chest X-ray (CXR) used to grade the extent of disease severity at diagnosis in patients with pulmonary tuberculosis (PTB) are often based on numerical scores that summate specific radiographic features. However, since PTB is known to exhibit a wide heterogeneity in pathology, certain features might be differentially associated with clinical parameters of disease severity.ObjectiveWe aimed to grade disease severity in PTB patients at diagnosis and after completion of DOTS treatment by developing a reading scheme based on five different radiographic manifestations and analyze their association with the clinical parameters of systemic involvement and infectivity.Methods141 HIV-negative adults with newly diagnosed sputum smear-positive PTB were enrolled in a prospective observational study in Hyderabad, India. The presence and extent on CXRs of five radiographic manifestations, i.e., lung involvement, alveolar infiltration, cavitation, lymphadenopathy and pleural effusion, were classified using the new reading scheme by using a four-quadrant approach. We evaluated the inter-reader reliability of each manifestation, and its association with BMI and sputum smear positivity at diagnosis. The presence and extent of these radiographic manifestations were further compared with CXRs on completion of DOTS treatment.ResultsAt diagnosis, an average lung area of 51.7% +/- 23.3% was affected by radiographic abnormalities. 94% of the patients had alveolar infiltrates, with 89.4% located in the upper quadrants, suggesting post primary PTB and in 34.8% of patients cavities were found. We further showed that the extent of affected lung area was a negative predictor of BMI (β value -0.035, p 0.019). No significant association of BMI with any of the other CXR features was found. The extent of alveolar infiltrates, along with the presence of cavitation, were strongly associated with sputum smear positivity. The microbiological cure rate in our cohort after 6 months of DOTS treatment was 95%. The extent of the affected lung area in these patients decreased from 56.0% +/- 21.5% to 31.0 +/- 20% and a decrease was also observed in the extent of alveolar infiltrates from 98.4% to 25.8% in at least one quadrant, presence of cavities from 34.8% to 1.6%, lymphadenopathy from 46.8% to 16.1%, and pleural effusion from 19.4% to 6.5%.ConclusionsWe established a new assessment scheme for grading disease severity in PTB by specifically considering five radiographic manifestations which were differently associated with the BMI and sputum smear positivity, changed to a different extent after 6 months of treatment and exhibited an excellent agreement between radiologists. Our results suggest that this reading scheme might contribute to the estimation of disease severity with respect to differences in disease pathology. Further studies are needed to determine a correlation with short and long-term pulmonary function impairment and whether there would be any benefit in lengthening or modulating therapy based on this...
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