Impact of diabetes mellitus on immunity to latent tuberculosis infection

Tuberculosis (TB) is an infectious disease that poses a major health threat and is one of the leading causes of death worldwide. Following exposure to Mycobacterium tuberculosis (M.tb) bacilli, hosts who fail to clear M.tb end up in a state of latent tuberculosis infection (LTBI), in which the bacteria are contained but not eliminated. Type 2 diabetes mellitus (DM) is a noncommunicable disease that can weaken host immunity and lead to increased susceptibility to various infectious diseases. Despite numerous studies on the relationship between DM and active TB, data on the association between DM and LTBI remains limited. Immunological data suggest that LTBI in the presence of DM leads to an impaired production of protective cytokines and poly-functional T cell responses, accounting for a potential immunological mechanism that could leads to an increased risk of active TB. This review highlights the salient features of the immunological underpinnings influencing the interaction between TB and DM in humans

Transcriptional Control of Impaired Th1 Responses in Patent Lymphatic Filariasis by T-Box Expressed in T Cells and Suppressor of Cytokine Signaling Genes

T-bet (T-box expressed in T cells) and GATA-3 are transcription factors that play a critical role in the development of Th1 and Th2 cells, as do genes of the SOCS (suppressor of cytokine signaling) family, albeit indirectly. Another transcription factor, Foxp3, is a master regulator of natural regulatory T cells (Tregs). To identify the role of these factors in impaired Th1 responses of patent filarial infection, analysis of cytokine, SOCS, and transcription factor mRNA expression was performed on purified T cells of filaria-infected individuals (n � 6) and uninfected controls (n � 6). As expected (and in contrast to cells of uninfected individuals), there was a significant depression of gamma interferon (IFN-�) and a concomitant increase in interleukin-4 (IL-4), IL-5, and IL-10 mRNA expression following stimulation with parasite antigen (BmA) but not with a polyclonal T-cell (anti-CD3) stimulus. T-bet (but not GATA-3) was expressed at significantly lower levels in cells of filaria-infected individuals in response to BmA compared with those from the uninfected group, accounting, at least partially, for the diminished IFN-� expression. Second, we found no significant differences in expression of Foxp3 between the two groups, although induction of Foxp3 expression correlated with induced expression levels of IL-10, implicating Tregs in the IL-10 expression seen. Finally, parasitespecific T-cell expression of SOCS-1, SOCS-5, and SOCS-7 was significantly diminished among infected patients; in contrast, expression of SOCS-3 increased. Our data therefore indicate that the impaired Th1 responses observed in patent lymphatic filariasis are associated with decreased expression of T-bet, SOCS-1, SOCS-5, and SOCS-7 and increased expression of SOCS-3 in T cells

Evaluation of maize genotypes against post flowering stalk rot under terai region of Nepal

The inadequate source of resistance materials in maize against major biotic stresses is one of the main reasons for considerable loss of grain yield in Nepal. Post flowering stalk rot disease caused by Fusarium moniliforme is a serious disease that exposes high incidence at grain filling stage of maize in terai region of Nepal during summer season. This study was done to evaluate level of resistance, or tolerance in selected genotypes against the post flowering stalk rot disease of maize. Accordingly, thirty maize genotypes were tested for maize stalk rot resistance during summer season of 2016 and 2017 at National Maize Research Program, Rampur (NMRP), Chitwan. The experiment was done under natural epiphytotic condition at hot spot of the disease by using Randomized Complete Block design with 2 replications for each treatment. The package of practices was followed as per national recommendation. The summer season of 2016 and 2017 were affable for post flowering stalk rot of maize at NMRP, Rampur. Out of 30 genotypes, most of the tested entries showed susceptible reaction during both the years; however, RML-95/RML-96, Across-9942/Across-9944, ZM-401, Rampur 34, RamS03F08 and TLBRS07F16 showed resistant reaction against the disease and might be useful for the development of post flowering stalk rot resistant maize varieties for terai region of Nepal

Helminth-Tuberculosis Co-infection: An Immunologic Perspective

Over 2 billion people worldwide are infected with helminths (worms). Similarly, infection with Mycobacterium tuberculosis (Mtb) occurs in over a third of the world's population, often with a great degree of geographical overlap with helminth infection. Interestingly, the responses induced by the extracellular helminths and those induced by the intracellular Mtb are often mutually antagonistic and, as a consequence, can result in impaired (or cross-regulated) host responses to either of the infecting pathogens. In this review, we outline the nature of the immune responses induced by infections with helminths and tuberculosis (TB) and then provide data from both experimental models and human studies that illustrate how the immune response engendered by helminth parasites modulates Mtb-specific responses in helminth-TB co-infection

Immunopathogenesis of lymphatic filarial disease

Although two-thirds of the 120 million people infected with lymph-dwelling filarial parasites have subclinical infections, ~ 40 million have lymphedema and/or other pathologic manifestations including hydroceles (and other forms of urogenital disease), episodic adenolymphangitis, tropical pulmonary eosinophilia, lymphedema, and (in its most severe form) elephantiasis. Adult filarial worms reside in the lymphatics and lymph nodes and induce changes that result in dilatation of lymphatics and thickening of the lymphatic vessel walls. Progressive lymphatic damage and pathology results from the summation of the effect of tissue alterations induced by both living and nonliving adult parasites, the host inflammatory response to the parasites and their secreted antigens, the host inflammatory response to the endosymbiont Wolbachia, and those seen as a consequence of secondary bacterial or fungal infections. Inflammatory damage induced by filarial parasites appears to be multifactorial, with endogenous parasite products, Wolbachia, and host immunity all playing important roles. This review will initially examine the prototypical immune responses engendered by the parasite and delineate the regulatory mechanisms elicited to prevent immune-mediated pathology. This will be followed by a discussion of the proposed mechanisms underlying pathogenesis, with the central theme being that pathogenesis is a two-step process - the first initiated by the parasite and host innate immune system and the second propagated mainly by the host’s adaptive immune system and by other factors (including secondary infections)

Elevated Systemic and Parasite—Antigen Stimulated Levels of Type III IFNs in a Chronic Helminth Infection and Reversal Following 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 Strongyloides stercoralis (Ss) infection, we examined the systemic levels of IFN lambda-1, IFN lambda-2 and IFN lambda-3, IL-10, and CXCL10/IP-10 in Ss infected (INF, n = 44), helminth—uninfected (UN, n = 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 Ss somatic antigens, or PPD or LPS. Finally, we performed correlations of systemic Type III IFN levels with absolute numbers of dendritic cell subsets. Ss 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. Ss infection is also characterized by elevated levels of unstimulated or Ss 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, Ss 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, Ss 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, Ss 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

Laboratory evaluation of a rapid IgG4 antibody test (BLF Rapid™) for bancroftian filariasis

At the end phase of the Global Programme to Eliminate Lymphatic Filariasis, antibody testing may have a role in decision-making for bancroftian filariasis–endemic areas. This study evaluated the diagnostic performance of BLF Rapid ™ , a prototype immunochromatographic IgG4-based test using BmSXP recombinant protein, for detection of bancroftian filariasis. The test was evaluated using 258 serum samples, comprising 96 samples tested at Universiti Sains Malaysia (in-house) and 162 samples tested independently at three international laboratories in the USA and India, and two laboratories in Malaysia. The independent testing involved 99 samples from Wuchereria bancrofti microfilaria or antigen positive individuals and 63 samples from people who were healthy or had other infections. The in-house evaluation showed 100% diagnostic sensitivity and specificity. The independent evaluations showed a diagnostic sensitivity of 84–100% and 100% specificity (excluding non-lymphatic filarial infections). BLF Rapid has potential as a surveillance diagnostic tool to make “Transmission Assessment Survey”–stopping decisions and conduct post-elimination surveillance