Human host defense against mycobacteria depends on a functioning immune system. While it is currently established that Th1 cells are major players in host defense against mycobacteria, other cell types such as Th17 cells also correlate strongly with the protective forms of disease. However, the role of Th17 cells in the context of intracellular infection are incompletely understood. Recent work has shown that Th17 cells can secrete an antimicrobial protein IL-26, which can directly lyse extracellular bacteria. Given the established role of antimicrobial peptides against mycobacterial infection, we decided to further investigate IL-26 and determine whether it is antimicrobial against mycobacteria. We find that IL-26 can be secreted by PBMCs and purified T cells in response to IL-1β in the absence of T cell receptor activation. This process is also more rapid than TCR stimulation. Among helper T cells, we show that IL-1RI expression was necessary for this response and identified IL-1RI+ Th17 cells as a cell type that can secrete IL-26 in response to IL-1β. Furthermore, we establish that IL-26 secreted in response to IL-1β is functionally antimicrobial.
We also examined whether IL-26 is antimicrobial against intracellular bacteria. We find that IL-26 is differentially expressed between clinical forms of leprosy, with higher expression in tuberculoid leprosy, the resistant form of the disease, as compared to lepromatous leprosy, the progressive form of the disease. Incubation of IL-26 with M. leprae and attenuated M. tuberculosis strain H37RA led to dose dependent killing, both with bacteria in culture and, importantly, while the bacteria resided within infected macrophages. Additionally, we find that IL-26 treatment of infected macrophages stimulates the autophagy response and enhances phagolysosome fusion in a STING dependent manner. Altogether, this work uncovers a novel mechanism by which Th17 cells contribute to defense against mycobacterial infection.
The relationship between tectonic environment and human activity has a long history that intimately involves the Ancient Near East and Levant. Texts from the third millennium onward attest to earthquake imagery while records of actual earthquakes cluster in two periods in the Middle and Neo-Assyrian periods. The research first examines the relationship between the tectonic environment and earthquake imagery that is found amidst Storm-god imagery. Next, close attention is paid to the textual and archaeoseismic evaluation of earthquakes recorded in Middle and Neo-Assyrian texts and the extent to which historical information from these texts can inform a reconstruction of the earthquake's effects. Within the Levant, a detailed archaeoseismic evaluation of Iron IIB sites with purported mid-eighth century seismic damage suggests better methodological controls are needed to identify seismic damage in the archaeological record. A number of interdisciplinary approaches, including post-disaster housing, earthquake eyewitness accounts, and gender and vulnerability studies are applied to Amos in order to provide a fresh perspective on identifying earthquake imagery within the book. These approaches help reconstruct the socioeconomic, political, and religious effects of the earthquake mentioned in Amos and illustrate how his oracles and prophetic validity would have been authenticated through the earthquake. These approaches also shed new light on "social justice" texts within Amos and how the aftermath of an earthquake would have underscored, anew, the gap between the rich and poor.
This dissertation looks at the effect of the arrival of cholera to the far northwestern province of Tucumán. This project participates in a relatively new historigraphical approach that has emerged within Latin American studies in the last decade: "sociocultural history of disease." I study the interaction between politics and culture, within the epidemics, in order to foreground the political agency of marginalized people and regions. The project determines the role that provincial politicians and public health played in center-periphery relations and the place of disease and health within the state-building project. I deviate from the literature on state-formation, which overemphasizes the role of the nation's capital and coercion, by highlighting the work of Tucumán in forming the Argentine state.
"Disease and Democracy" analyzes the relationship between province and state through the study of two cholera epidemics in 1868 and 1886. Through an analysis of medical dissertations, newspapers, government reports, memoirs, traveler reports, private correspondence, songs, tales and stories examined in libraries and archives in Buenos Aires, La Plata, Córdoba and Tucumán, I utilize the epidemics as a lens through which I explore the fractious relationship between politics and health. Studying epidemics is especially productive because the stress that epidemics place on society illuminates areas of the social fabric that would otherwise go unnoticed. My research reveals multiple instances in which the provinces took the lead in creating services and institutions that established the presence of the state in the interior, and created a balance between the needs of the state and provincial autonomy.
The eighteenth century in the Afro-Luso-Brazilian world was a time of depopulation anxiety and pressure towards epistemic, political, and imperial reform. Configurations of the Human tracks how the struggle to produce a new and more vigorous people dovetailed in clashes about social power and epistemic preeminence inflected in distinct worldviews about the status of the human. From an object of divine creation to a species, this dissertation tracks a shift from the dominance of religion to medicine as the dominant languages of knowledge about the natural world. The struggle for modern reform, a term used in the eighteenth century by several protagonists recovered here, hinged on an effort to replace Church power and Scholastic methods for modern medical approaches. Despite the enforcement of modern epistemic transformations, the modern medical method continued to recapitulate patriarchal models of power while simultaneously seeking to intercede with the patriarch, thus rendering him into the first agent of modern reform. Throughout five chapters, I reveal how projects of population multiplication in Lisbon traveled to the Amazon to build better population futures. I do this by theorizing the household (casa) as a patriarchal technology of medical power, race, reproduction, and political economy. Tracing the origins of state-sponsored racial whitening in Portugal and Brazil, I offer the first study of relational racial production in the Afro-Luso-Brazilian Atlantic. This work historicizes the medicalization of race, “sex,” education, and patriarchal power. Conditions of possibility for whitening, I argue, stemmed from theories of generation positing “male seed” as the active seat of logos and female “wombs” as passive matter. Under the rule of white patriarchs, subalterns in Portugal and Amerindians in the Amazon would metamorph into “white vassals.” However, the population’s procreative imperative also inflicted exclusions. Namely, female same-sex desire became a cognitive impossibility for its refusal of reproductive futurity. Similarly, Blackness also became incommensurate with Portuguese civilization. Showing how abolitionism hinged on Portugal’s whitening—the “blackest” European capital—I analyze how the pathologization of Black women was critical to preserving South Atlantic slavery at a time of rising abolitionist pressures
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