RESUMEN

Carbon nanotubes (CNTs) are emerging pollutants of occupational and environmental health concern. While toxicological mechanisms of CNTs are emerging, there is paucity of information on their modulatory effects on susceptibility to infections. Here, we investigated cellular and molecular events underlying the effect of multi-walled CNT (MWCNT) exposure on susceptibility to Streptococcus pneumoniae infection in our 28-day sub-chronic exposure mouse model. Data indicated reduced phagocytic function in alveolar macrophages (AMs) from MWCNT-exposed lungs evidenced by lower pathogen uptake in 1-h infection assay. At 24-h post-infection, intracellular pathogen count in exposed AMs showed 2.5 times higher net increase (2-fold in vehicle- versus 5-fold in MWCNT-treated), indicating a greater rate of intracellular multiplication and/or survival due to MWCNT exposure. AMs from MWCNT-exposed lungs exhibited downregulation of pathogen-uptake receptors CD163, Phosphatidyl-serine receptor (Ptdsr), and Macrophage scavenger receptors class A type 1 (Msr1) and type 2 (MSr2). In whole lung, MWCNT exposure shifted the macrophage polarization state towards the immunosuppressive phenotype M2b and increased the CD11c+ dendritic cell population required to activate the adaptive immune response. Notably, the MWCNT pre-exposure dysregulated T-cell immunity, evidenced by diminished CD4 and Th17 response, and exacerbated Th1 and Treg responses (skewed Th17/Treg ratio), thereby favoring the pneumococcal infection. Overall, these findings indicated that MWCNT exposure compromises both innate and adaptive immunity leading to diminished host lung defense against pneumonia infection. To our knowledge, this is the first report on an immunomodulatory role of CNT pre-exposure on pneumococcal infection susceptibility due to dysregulation of both innate and adaptive immunity targets.

Asunto(s)

Nanopartículas , Nanotubos de Carbono , Neumonía Neumocócica , Ratones , Animales , Nanotubos de Carbono/toxicidad , Ratones Endogámicos C57BL , Pulmón , Inmunidad , Nanopartículas/toxicidad

RESUMEN

The role of women in science and technology has become crucial for the overall development of a nation. In India, the numeric representation of women up to graduate and postgraduate levels is the same as male candidates but declines from the doctorate level. A continued women's lower employment rate in universities and higher educational institutes must be analyzed for necessary action. The Government of India has initiated various schemes, programs, fellowships, and financial grants to the research community to carry out basic and advanced scientific and technological research. In this regard, the present study maps the participation of women through research proposal submission and approval in selected schemes of the Science and Engineering Research Board (SERB). The study also analyzed subject-wise trends and the role of institutes in developing the capacities of women scientists to perform research in cutting-edge technologies. The paper also describes the impact of SERB's women-centric POWER Scheme to uplift women scientists from different institutes. The review recommends potential areas where women researchers should be further encouraged to participate and generate solutions for societal problems using the tools of science and technology.

RESUMEN

Inhaled toxic chemicals and particulates are known to disrupt lung homeostasis causing pulmonary toxicity and tissue injury. However, biomarkers of such exposures and their underlying mechanisms are poorly understood, especially for emerging toxicants such as engineered nanoparticles and chemical threat agents such as chlorine gas (Cl2). Aquaporins (AQPs), commonly referred to as water channels, are known to play roles in lung homeostasis and pathophysiology. However, little is known on their regulation in toxicant-induced lung injuries. Here, we compared four lung toxicity models namely, acute chemical exposure (Cl2)-, chronic particulate exposure (carbon nanotubes/CNT)-, chronic chemical exposure (cigarette smoke extract/CSE)-, and a chronic co-exposure (CNT + CSE)- model, for modulation of lung aquaporins (AQPs 1, 3, 4, and 5) in relation to other pathophysiological endpoints. These included markers of compromised state of lung mucosal lining [mucin 5b (MUC5B) and surfactant protein A (SP-A)] and lung-blood barrier [protein content in bronchoalveolar lavage (BAL) fluid and, cell tight junction proteins occludin and zona-occludens]. The results showed toxicity model-specific regulation of AQPs measured in terms of mRNA abundance. A differential upregulation was observed for AQP1 in acute Cl2 exposure model (14.71-fold; p = 0.002) and AQP3 in chronic CNT exposure model (3.83-fold; p = 0.044). In contrast, AQP4 was downregulated in chronic CSE model whereas AQP5 showed no significant change in any of the models. SP-A and MUC5B expression showed a decreasing pattern across all toxicity models except the acute Cl2 toxicity model, which showed a highly significant upregulation of MUC5B (25.95-fold; p = 0.003). This was consistent with other significant pathophysiological changes observed in this acute model, particularly a compromised lung epithelial-endothelial barrier indicated by significantly increased protein infiltration and expression of tight junction proteins, and more severe histopathological (structural and immunological) changes. To our knowledge, this is the first report on lung AQPs as molecular targets of the study toxicants. The differentially regulated AQPs, AQP1 in acute Cl2 exposure versus AQP3 in chronic CNT nanoparticle exposure, in conjunction with the corresponding differentially impacted pathophysiological endpoints (particularly MUC5B) could potentially serve as predictive markers of toxicant type-specific pulmonary injury and as candidates for future investigation for clinical intervention.