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Recovery from respiratory pneumococcal infections generates lung-localized protection against heterotypic bacteria, mediated by resident memory lymphocytes. Optimal protection in mice requires re-exposure to pneumococcus within days of initial infection. Serial surface marker phenotyping of B cell populations in a model of pneumococcal heterotypic immunity revealed that bacterial re-exposure stimulates the immediate accumulation of dynamic and heterogeneous populations of B cells in the lung, and is essential for the establishment of lung resident memory B (B RM ) cells. The B cells in the early wave were activated, proliferating locally, and associated with both CD4 + T cells and CXCL13. Antagonist- and antibody-mediated interventions were implemented during this early timeframe to demonstrate that lymphocyte recirculation, CD4 + cells, and CD40 ligand (CD40L) signaling were all needed for lung B RM cell establishment, whereas CXCL13 signaling was not. While most prominent as aggregates in the loose connective tissue of bronchovascular bundles, morphometry and live lung imaging analyses showed that lung B RM cells were equally numerous as single cells dispersed throughout the alveolar septae. We propose that CD40L signaling from antigen-stimulated CD4 + T cells in the infected lung is critical to establishment of local B RM cells, which subsequently protect the airways and parenchyma against future potential infections., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Etesami, Barker, Shenoy, De Ana, Arafa, Grifno, Matschulat, Vannini, Pihl, Breen, Soucy, Goltry, Ha, Betsuyaku, Browning, Varelas, Traber, Jones, Quinton, Maglione, Nia, Belkina and Mizgerd.)

Streptococcus pneumoniae is the most common etiology of bacterial pneumonia, one of the leading causes of death in children and the elderly worldwide. During non-lethal infections with S. pneumoniae, lymphocytes accumulate in the lungs and protect against reinfection with serotype-mismatched strains. Cluster of differentiation CD4 + resident memory T (T RM ) cells are known to be crucial for this protection, but the diversity of lung CD4 + T RM cells has yet to be fully delineated. We aimed to identify unique subsets and their contributions to lung immunity. After recovery from pneumococcal infections, we identified a distinct subset of CD4 + T cells defined by the phenotype CD11a hi CD69 + GL7 + in mouse lungs. Phenotypic analyses for markers of lymphocyte memory and residence demonstrated that GL7 + T cells are a subset of CD4 + T RM cells. Functional studies revealed that unlike GL7 - T RM subsets that were mostly (RAR-related Orphan Receptor gamma T) RORγT + , GL7 + T RM cells exhibited higher levels of (T-box expressed in T cells) T-bet and Gata-3, corresponding with increased synthesis of interferon-γ, interleukin-13, and interleukin-5, inherent to both T helper 1 (T H 1) and T H 2 functions. Thus, we propose that these cells provide novel contributions during pneumococcal pneumonia, serving as important determinants of lung immunity., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

The great demand on the energy makes the attention toward modifying lubricating oil. This work tends to prepare the following copolymers; octadecylmethacrylate-co-dodecene (CP 1 ) and octadecylmethacrylate-co-hexadecene (CP 2 ) by free radical solution polymerization using laboratory prepared octadecylmethacrylate monomer with either 1-dodecene or 1-hexadecene. The same monomers also used to prepare their polymers nanocomposite (NP 1 , NP 2 ) with 1% of nanomontmorolonite by emulsion polymerization. The structures of the prepared polymers and their nanocomposite were elucidated by FTIR, 1 HNMR, TGA, DSC, TEM and DLS. These polymers were used as pour point depressant, flow improver and viscosity modifier and showed high efficiency. After comparison of the data of the polymers and their nanocomposite, the nanocomposite give the best results where the pour point decreased from 0 °C to - 18, - 27, - 24 and - 33 °C for CP 1 , CP 2 , NP 1 and NP 2 respectively at the optimum concentration 10,000 ppm. On the other hand the viscosity index increased from 86.57 to 93.25, 92.41, 94.17 and 93.103 for CP 1 , CP 2 , NP 1 and NP 2 respectively, the apparent viscosity increased from 55.863 to 69.31, 119.41, 111.28, and 166.89 cP also the yield stress increased from 652.19 to 1076.3, 1074 and 1480 D/cm 2 for CP 1 , CP 2 , NP 1 and NP 2 respectively., (© 2023. Springer Nature Limited.)

Identifying host factors that contribute to pneumonia incidence and severity are of utmost importance to guiding the development of more effective therapies. Lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1, encoded by OLR1) is a scavenger receptor known to promote vascular injury and inflammation, but whether and how LOX-1 functions in the lung are unknown. Here, we provide evidence of substantial accumulation of LOX-1 in the lungs of patients with acute respiratory distress syndrome and in mice with pneumonia. Unlike previously described injurious contributions of LOX-1, we found that LOX-1 is uniquely protective in the pulmonary airspaces, limiting proteinaceous edema and inflammation. We also identified alveolar macrophages and recruited neutrophils as 2 prominent sites of LOX-1 expression in the lungs, whereby macrophages are capable of further induction during pneumonia and neutrophils exhibit a rapid, but heterogenous, elevation of LOX-1 in the infected lung. Blockade of LOX-1 led to dysregulated immune signaling in alveolar macrophages, marked by alterations in activation markers and a concomitant elevation of inflammatory gene networks. However, bone marrow chimeras also suggested a prominent role for neutrophils in LOX-1-mediated lung protection, further supported by LOX-1+ neutrophils exhibiting transcriptional changes consistent with reparative processes. Taken together, this work establishes LOX-1 as a tissue-protective factor in the lungs during pneumonia, possibly mediated by its influence on immune signaling in alveolar macrophages and LOX-1+ airspace neutrophils.

Recovery from pneumococcal (Spn) pneumonia induces development of tissue resident memory CD4 + T RM cells, B RM cells, and antibody secreting plasma cells in experienced lungs. These tissue resident lymphocytes confer protection against subsequent lethal challenge by serotype mismatched Spn (termed as heterotypic immunity). While traditional flow cytometry and gating strategies support premeditated identification of cells using a limited set of markers, discovery of novel tissue resident lymphocytes necessitates stable platforms that can handle larger sets of phenotypic markers and lends itself to unbiased clustering approaches. In this report, we leverage the power of full spectrum flow cytometry (FSFC) to develop a comprehensive panel of phenotypic markers that allows identification of multiple subsets of tissue resident lymphocytes in Spn-experienced murine lungs. Using Phenograph algorithm on this multidimensional data, we identify unforeseen heterogeneity in lung resident adaptive immune landscape which includes unexpected subsets of T RM and B RM cells. Further, using conventional gating strategy informed by our unsupervised clustering data, we confirm their presence exquisitely in Spn-experienced lungs as potentially relevant to heterotypic immunity and define CD73 as a highly expressed marker on T RM cells. Thus, our study emphasizes the utility of FSFC for confirmatory and discovery studies relating to tissue resident adaptive immunity., (© 2021 International Society for Advancement of Cytometry.)

Recovery from pneumococcal pneumonia remodels the pool of alveolar macrophages so that they exhibit new surface marker profiles, transcriptomes, metabolomes, and responses to infection. Mechanisms mediating alveolar macrophage phenotypes after pneumococcal pneumonia have not been delineated. IFN-γ and its receptor on alveolar macrophages were essential for certain, but not all, aspects of the remodeled alveolar macrophage phenotype. IFN-γ was produced by CD4+ T cells plus other cells, and CD4+ cell depletion did not prevent alveolar macrophage remodeling. In mice infected or recovering from pneumococcus, monocytes were recruited to the lungs, and the monocyte-derived macrophages developed characteristics of alveolar macrophages. CCR2 mediated the early monocyte recruitment but was not essential to the development of the remodeled alveolar macrophage phenotype. Lineage tracing demonstrated that recovery from pneumococcal pneumonias converted the pool of alveolar macrophages from being primarily of embryonic origin to being primarily of adult hematopoietic stem cell origin. Alveolar macrophages of either origin demonstrated similar remodeled phenotypes, suggesting that ontogeny did not dictate phenotype. Our data reveal that the remodeled alveolar macrophage phenotype in lungs recovered from pneumococcal pneumonia results from a combination of new recruitment plus training of both the original cells and the new recruits.