Secretory Aspartyl Proteinases Cause Vaginitis and Can Mediate Vaginitis Caused by Candida albicans in Mice

Vaginal inflammation (vaginitis) is the most common disease caused by the human-pathogenic fungus Candida albicans. Secretory aspartyl proteinases (Sap) are major virulence traits of C. albicans that have been suggested to play a role in vaginitis. To dissect the mechanisms by which Sap play this role, Sap2, a dominantly expressed member of the Sap family and a putative constituent of an anti-Candida vaccine, was used. Injection of full-length Sap2 into the mouse vagina caused local neutrophil influx and accumulation of the inflammasome-dependent interleukin-1β (IL-1β) but not of inflammasome-independent tumor necrosis factor alpha. Sap2 could be replaced by other Sap, while no inflammation was induced by the vaccine antigen, the N-terminal-truncated, enzymatically inactive tSap2. Anti-Sap2 antibodies, in particular Fab from a human combinatorial antibody library, inhibited or abolished the inflammatory response, provided the antibodies were able, like the Sap inhibitor Pepstatin A, to inhibit Sap enzyme activity. The same antibodies and Pepstatin A also inhibited neutrophil influx and cytokine production stimulated by C. albicans intravaginal injection, and a mutant strain lacking SAP1, SAP2, and SAP3 was unable to cause vaginal inflammation. Sap2 induced expression of activated caspase-1 in murine and human vaginal epithelial cells. Caspase-1 inhibition downregulated IL-1β and IL-18 production by vaginal epithelial cells, and blockade of the IL-1β receptor strongly reduced neutrophil influx. Overall, the data suggest that some Sap, particularly Sap2, are proinflammatory proteins in vivo and can mediate the inflammasome-dependent, acute inflammatory response of vaginal epithelial cells to C. albicans. These findings support the notion that vaccine-induced or passively administered anti-Sap antibodies could contribute to control vaginitis

The Fungal Pathogen Candida glabrata Does Not Depend on Surface Ferric Reductases for Iron Acquisition

Iron acquisition is a crucial virulence determinant for many bacteria and fungi, including the opportunistic fungal pathogens Candida albicans and C. glabrata. While the diverse strategies used by C. albicans for obtaining iron from the host are well-described, much less is known about the acquisition of this micronutrient from host sources by C. glabrata – a distant relative of C. albicans with closer evolutionary ties to Saccharomyces cerevisiae, which nonetheless causes severe clinical symptoms in humans. Here we show that C. glabrata is much more restricted than C. albicans in using host iron sources, lacking, for example, the ability to grow on transferrin and hemin/hemoglobin. Instead, C. glabrata is able to use ferritin and non-protein-bound iron (FeCl3) as iron sources in a pH-dependent manner. As in other fungal pathogens, iron-dependent growth requires the reductive high affinity (HA) iron uptake system. Typically highly conserved, this uptake mechanism normally relies on initial ferric reduction by cell-surface ferric reductases. The C. glabrata genome contains only three such putative ferric reductases, which were found to be dispensable for iron-dependent growth. In addition and in contrast to C. albicans and S. cerevisiae, we also detected no surface ferric reductase activity in C. glabrata. Instead, extracellular ferric reduction was found in this and the two other fungal species, which was largely dependent on an excreted low-molecular weight, non-protein ferric reductant. We therefore propose an iron acquisition strategy of C. glabrata which differs from other pathogenic fungi, such as C. albicans, in that it depends on a limited set of host iron sources and that it lacks the need for surface ferric reductases. Extracellular ferric reduction by a secreted molecule possibly compensates for the loss of surface ferric reductase activity in the HA iron uptake system

The fungal peptide toxin Candidalysin activates the NLRP3 inflammasome and causes cytolysis in mononuclear phagocytes

Clearance of invading microbes requires phagocytes of the innate immune system. However, successful pathogens have evolved sophisticated strategies to evade immune killing. The opportunistic human fungal pathogen Candida albicans is efficiently phagocytosed by macrophages, but causes inflammasome activation, host cytolysis, and escapes after hypha formation. Previous studies suggest that macrophage lysis by C. albicans results from early inflammasome-dependent cell death (pyroptosis), late damage due to glucose depletion and membrane piercing by growing hyphae. Here we show that Candidalysin, a cytolytic peptide toxin encoded by the hypha-associated gene ECE1, is both a central trigger for NLRP3 inflammasome-dependent caspase-1 activation via potassium efflux and a key driver of inflammasome-independent cytolysis of macrophages and dendritic cells upon infection with C. albicans. This suggests that Candidalysin-induced cell damage is a third mechanism of C. albicans-mediated mononuclear phagocyte cell death in addition to damage caused by pyroptosis and the growth of glucose-consuming hyphae

African linguistics across the disciplines: Selected papers from the 48th Annual Conference on African Linguistics

Since the hiring of its first Africanist linguist Carleton Hodge in 1964, Indiana University’s Department of Linguistics has had a strong and continuing presence in the study of African languages and linguistics through the work of its faculty and of its graduates on the faculties of many other universities. Research on African linguistics at IU has covered some of the major language groups spoken on the African continent. Carleton Hodge’s work on Ancient Egyptian and Hausa, Paul Newman’s work on Hausa and Chadic languages, and Roxanna Ma Newman’s work on Hausa language structure and pedagogy have been some of the most important studies on Afro-Asiatic linguistics. With respect to Niger-Congo languages, the work of Charles Bird on Bambara and the Mande languages, Robert Botne’s work on Bantu structure (especially tense and aspect), Samuel Obeng and Colin Painter’s work on Ghanaian Languages (phonetics, phonology, and pragmatics), Robert Port’s studies on Swahili, and Erhard Voeltz's studies on Bantu linguistics are considered some of the most influential studies in the sub-field. On Nilo Saharan languages, the work of Tim Shopen on Songhay stands out. IU Linguistics has also forwarded theoretical work on African languages, such as John Goldsmith’s seminal research on tone in African languages. The African linguistics faculty at IU have either founded or edited important journals in African Studies, African languages, and African linguistics, including Africa Today, Studies in African Linguistics, and Journal of African Languages and Linguistics. In 1972, the Indiana University Department of Linguistics hosted the Third Annual Conference of African Linguistics. Proceedings of that conference were published by Indiana University Publications (African Series, vol. 7). In 1986, IU hosted the Seventeenth Annual Conference of African Linguistics with Paul Newman and Robert Botne editing the proceedings in a volume entitled Current Approaches to African Linguistics, vol. 5. In 2016, Indiana University hosted the 48th Annual Conference on African Linguistics with the theme African Linguistics Across the Disciplines. Proceedings of that meeting are published in this volume. The papers presented in this volume reflect the diversity of opportunities for language study in Africa. This collection of descriptive and theoretical work is the fruit of data gathering both in-country and abroad by researchers of languages spoken across the continent, from Sereer-sin in the west to Somali in the northeast to Ikalanga in the south. The range of topics in this volume is also broad, representative of the varied field work in country and abroad that inspires research in African linguistics. This collection of papers spans the disciplines of phonology (both segmental and suprasegmental), morphology (both morphophonological and morphosyntactic), syntax, semantics, and language policy. The data and analyses presented in this volume offer a cross-disciplinary view of linguistic topics from the many under-resourced languages of Africa

African linguistics across the disciplines: Selected papers from the 48th Annual Conference on African Linguistics

Since the hiring of its first Africanist linguist Carleton Hodge in 1964, Indiana University’s Department of Linguistics has had a strong and continuing presence in the study of African languages and linguistics through the work of its faculty and of its graduates on the faculties of many other universities. Research on African linguistics at IU has covered some of the major language groups spoken on the African continent. Carleton Hodge’s work on Ancient Egyptian and Hausa, Paul Newman’s work on Hausa and Chadic languages, and Roxanna Ma Newman’s work on Hausa language structure and pedagogy have been some of the most important studies on Afro-Asiatic linguistics. With respect to Niger-Congo languages, the work of Charles Bird on Bambara and the Mande languages, Robert Botne’s work on Bantu structure (especially tense and aspect), Samuel Obeng and Colin Painter’s work on Ghanaian Languages (phonetics, phonology, and pragmatics), Robert Port’s studies on Swahili, and Erhard Voeltz's studies on Bantu linguistics are considered some of the most influential studies in the sub-field. On Nilo Saharan languages, the work of Tim Shopen on Songhay stands out. IU Linguistics has also forwarded theoretical work on African languages, such as John Goldsmith’s seminal research on tone in African languages. The African linguistics faculty at IU have either founded or edited important journals in African Studies, African languages, and African linguistics, including Africa Today, Studies in African Linguistics, and Journal of African Languages and Linguistics. In 1972, the Indiana University Department of Linguistics hosted the Third Annual Conference of African Linguistics. Proceedings of that conference were published by Indiana University Publications (African Series, vol. 7). In 1986, IU hosted the Seventeenth Annual Conference of African Linguistics with Paul Newman and Robert Botne editing the proceedings in a volume entitled Current Approaches to African Linguistics, vol. 5. In 2016, Indiana University hosted the 48th Annual Conference on African Linguistics with the theme African Linguistics Across the Disciplines. Proceedings of that meeting are published in this volume. The papers presented in this volume reflect the diversity of opportunities for language study in Africa. This collection of descriptive and theoretical work is the fruit of data gathering both in-country and abroad by researchers of languages spoken across the continent, from Sereer-sin in the west to Somali in the northeast to Ikalanga in the south. The range of topics in this volume is also broad, representative of the varied field work in country and abroad that inspires research in African linguistics. This collection of papers spans the disciplines of phonology (both segmental and suprasegmental), morphology (both morphophonological and morphosyntactic), syntax, semantics, and language policy. The data and analyses presented in this volume offer a cross-disciplinary view of linguistic topics from the many under-resourced languages of Africa

African linguistics across the disciplines: Selected papers from the 48th Annual Conference on African Linguistics

Since the hiring of its first Africanist linguist Carleton Hodge in 1964, Indiana University’s Department of Linguistics has had a strong and continuing presence in the study of African languages and linguistics through the work of its faculty and of its graduates on the faculties of many other universities. Research on African linguistics at IU has covered some of the major language groups spoken on the African continent. Carleton Hodge’s work on Ancient Egyptian and Hausa, Paul Newman’s work on Hausa and Chadic languages, and Roxanna Ma Newman’s work on Hausa language structure and pedagogy have been some of the most important studies on Afro-Asiatic linguistics. With respect to Niger-Congo languages, the work of Charles Bird on Bambara and the Mande languages, Robert Botne’s work on Bantu structure (especially tense and aspect), Samuel Obeng and Colin Painter’s work on Ghanaian Languages (phonetics, phonology, and pragmatics), Robert Port’s studies on Swahili, and Erhard Voeltz's studies on Bantu linguistics are considered some of the most influential studies in the sub-field. On Nilo Saharan languages, the work of Tim Shopen on Songhay stands out. IU Linguistics has also forwarded theoretical work on African languages, such as John Goldsmith’s seminal research on tone in African languages. The African linguistics faculty at IU have either founded or edited important journals in African Studies, African languages, and African linguistics, including Africa Today, Studies in African Linguistics, and Journal of African Languages and Linguistics. In 1972, the Indiana University Department of Linguistics hosted the Third Annual Conference of African Linguistics. Proceedings of that conference were published by Indiana University Publications (African Series, vol. 7). In 1986, IU hosted the Seventeenth Annual Conference of African Linguistics with Paul Newman and Robert Botne editing the proceedings in a volume entitled Current Approaches to African Linguistics, vol. 5. In 2016, Indiana University hosted the 48th Annual Conference on African Linguistics with the theme African Linguistics Across the Disciplines. Proceedings of that meeting are published in this volume. The papers presented in this volume reflect the diversity of opportunities for language study in Africa. This collection of descriptive and theoretical work is the fruit of data gathering both in-country and abroad by researchers of languages spoken across the continent, from Sereer-sin in the west to Somali in the northeast to Ikalanga in the south. The range of topics in this volume is also broad, representative of the varied field work in country and abroad that inspires research in African linguistics. This collection of papers spans the disciplines of phonology (both segmental and suprasegmental), morphology (both morphophonological and morphosyntactic), syntax, semantics, and language policy. The data and analyses presented in this volume offer a cross-disciplinary view of linguistic topics from the many under-resourced languages of Africa

African linguistics across the disciplines: Selected papers from the 48th Annual Conference on African Linguistics

Since the hiring of its first Africanist linguist Carleton Hodge in 1964, Indiana University’s Department of Linguistics has had a strong and continuing presence in the study of African languages and linguistics through the work of its faculty and of its graduates on the faculties of many other universities. Research on African linguistics at IU has covered some of the major language groups spoken on the African continent. Carleton Hodge’s work on Ancient Egyptian and Hausa, Paul Newman’s work on Hausa and Chadic languages, and Roxanna Ma Newman’s work on Hausa language structure and pedagogy have been some of the most important studies on Afro-Asiatic linguistics. With respect to Niger-Congo languages, the work of Charles Bird on Bambara and the Mande languages, Robert Botne’s work on Bantu structure (especially tense and aspect), Samuel Obeng and Colin Painter’s work on Ghanaian Languages (phonetics, phonology, and pragmatics), Robert Port’s studies on Swahili, and Erhard Voeltz's studies on Bantu linguistics are considered some of the most influential studies in the sub-field. On Nilo Saharan languages, the work of Tim Shopen on Songhay stands out. IU Linguistics has also forwarded theoretical work on African languages, such as John Goldsmith’s seminal research on tone in African languages. The African linguistics faculty at IU have either founded or edited important journals in African Studies, African languages, and African linguistics, including Africa Today, Studies in African Linguistics, and Journal of African Languages and Linguistics. In 1972, the Indiana University Department of Linguistics hosted the Third Annual Conference of African Linguistics. Proceedings of that conference were published by Indiana University Publications (African Series, vol. 7). In 1986, IU hosted the Seventeenth Annual Conference of African Linguistics with Paul Newman and Robert Botne editing the proceedings in a volume entitled Current Approaches to African Linguistics, vol. 5. In 2016, Indiana University hosted the 48th Annual Conference on African Linguistics with the theme African Linguistics Across the Disciplines. Proceedings of that meeting are published in this volume. The papers presented in this volume reflect the diversity of opportunities for language study in Africa. This collection of descriptive and theoretical work is the fruit of data gathering both in-country and abroad by researchers of languages spoken across the continent, from Sereer-sin in the west to Somali in the northeast to Ikalanga in the south. The range of topics in this volume is also broad, representative of the varied field work in country and abroad that inspires research in African linguistics. This collection of papers spans the disciplines of phonology (both segmental and suprasegmental), morphology (both morphophonological and morphosyntactic), syntax, semantics, and language policy. The data and analyses presented in this volume offer a cross-disciplinary view of linguistic topics from the many under-resourced languages of Africa

African linguistics across the disciplines: Selected papers from the 48th Annual Conference on African Linguistics

Since the hiring of its first Africanist linguist Carleton Hodge in 1964, Indiana University’s Department of Linguistics has had a strong and continuing presence in the study of African languages and linguistics through the work of its faculty and of its graduates on the faculties of many other universities. Research on African linguistics at IU has covered some of the major language groups spoken on the African continent. Carleton Hodge’s work on Ancient Egyptian and Hausa, Paul Newman’s work on Hausa and Chadic languages, and Roxanna Ma Newman’s work on Hausa language structure and pedagogy have been some of the most important studies on Afro-Asiatic linguistics. With respect to Niger-Congo languages, the work of Charles Bird on Bambara and the Mande languages, Robert Botne’s work on Bantu structure (especially tense and aspect), Samuel Obeng and Colin Painter’s work on Ghanaian Languages (phonetics, phonology, and pragmatics), Robert Port’s studies on Swahili, and Erhard Voeltz's studies on Bantu linguistics are considered some of the most influential studies in the sub-field. On Nilo Saharan languages, the work of Tim Shopen on Songhay stands out. IU Linguistics has also forwarded theoretical work on African languages, such as John Goldsmith’s seminal research on tone in African languages. The African linguistics faculty at IU have either founded or edited important journals in African Studies, African languages, and African linguistics, including Africa Today, Studies in African Linguistics, and Journal of African Languages and Linguistics. In 1972, the Indiana University Department of Linguistics hosted the Third Annual Conference of African Linguistics. Proceedings of that conference were published by Indiana University Publications (African Series, vol. 7). In 1986, IU hosted the Seventeenth Annual Conference of African Linguistics with Paul Newman and Robert Botne editing the proceedings in a volume entitled Current Approaches to African Linguistics, vol. 5. In 2016, Indiana University hosted the 48th Annual Conference on African Linguistics with the theme African Linguistics Across the Disciplines. Proceedings of that meeting are published in this volume. The papers presented in this volume reflect the diversity of opportunities for language study in Africa. This collection of descriptive and theoretical work is the fruit of data gathering both in-country and abroad by researchers of languages spoken across the continent, from Sereer-sin in the west to Somali in the northeast to Ikalanga in the south. The range of topics in this volume is also broad, representative of the varied field work in country and abroad that inspires research in African linguistics. This collection of papers spans the disciplines of phonology (both segmental and suprasegmental), morphology (both morphophonological and morphosyntactic), syntax, semantics, and language policy. The data and analyses presented in this volume offer a cross-disciplinary view of linguistic topics from the many under-resourced languages of Africa

African linguistics across the disciplines: Selected papers from the 48th Annual Conference on African Linguistics

Since the hiring of its first Africanist linguist Carleton Hodge in 1964, Indiana University’s Department of Linguistics has had a strong and continuing presence in the study of African languages and linguistics through the work of its faculty and of its graduates on the faculties of many other universities. Research on African linguistics at IU has covered some of the major language groups spoken on the African continent. Carleton Hodge’s work on Ancient Egyptian and Hausa, Paul Newman’s work on Hausa and Chadic languages, and Roxanna Ma Newman’s work on Hausa language structure and pedagogy have been some of the most important studies on Afro-Asiatic linguistics. With respect to Niger-Congo languages, the work of Charles Bird on Bambara and the Mande languages, Robert Botne’s work on Bantu structure (especially tense and aspect), Samuel Obeng and Colin Painter’s work on Ghanaian Languages (phonetics, phonology, and pragmatics), Robert Port’s studies on Swahili, and Erhard Voeltz's studies on Bantu linguistics are considered some of the most influential studies in the sub-field. On Nilo Saharan languages, the work of Tim Shopen on Songhay stands out. IU Linguistics has also forwarded theoretical work on African languages, such as John Goldsmith’s seminal research on tone in African languages. The African linguistics faculty at IU have either founded or edited important journals in African Studies, African languages, and African linguistics, including Africa Today, Studies in African Linguistics, and Journal of African Languages and Linguistics. In 1972, the Indiana University Department of Linguistics hosted the Third Annual Conference of African Linguistics. Proceedings of that conference were published by Indiana University Publications (African Series, vol. 7). In 1986, IU hosted the Seventeenth Annual Conference of African Linguistics with Paul Newman and Robert Botne editing the proceedings in a volume entitled Current Approaches to African Linguistics, vol. 5. In 2016, Indiana University hosted the 48th Annual Conference on African Linguistics with the theme African Linguistics Across the Disciplines. Proceedings of that meeting are published in this volume. The papers presented in this volume reflect the diversity of opportunities for language study in Africa. This collection of descriptive and theoretical work is the fruit of data gathering both in-country and abroad by researchers of languages spoken across the continent, from Sereer-sin in the west to Somali in the northeast to Ikalanga in the south. The range of topics in this volume is also broad, representative of the varied field work in country and abroad that inspires research in African linguistics. This collection of papers spans the disciplines of phonology (both segmental and suprasegmental), morphology (both morphophonological and morphosyntactic), syntax, semantics, and language policy. The data and analyses presented in this volume offer a cross-disciplinary view of linguistic topics from the many under-resourced languages of Africa

African linguistics across the disciplines: Selected papers from the 48th Annual Conference on African Linguistics

Since the hiring of its first Africanist linguist Carleton Hodge in 1964, Indiana University’s Department of Linguistics has had a strong and continuing presence in the study of African languages and linguistics through the work of its faculty and of its graduates on the faculties of many other universities. Research on African linguistics at IU has covered some of the major language groups spoken on the African continent. Carleton Hodge’s work on Ancient Egyptian and Hausa, Paul Newman’s work on Hausa and Chadic languages, and Roxanna Ma Newman’s work on Hausa language structure and pedagogy have been some of the most important studies on Afro-Asiatic linguistics. With respect to Niger-Congo languages, the work of Charles Bird on Bambara and the Mande languages, Robert Botne’s work on Bantu structure (especially tense and aspect), Samuel Obeng and Colin Painter’s work on Ghanaian Languages (phonetics, phonology, and pragmatics), Robert Port’s studies on Swahili, and Erhard Voeltz's studies on Bantu linguistics are considered some of the most influential studies in the sub-field. On Nilo Saharan languages, the work of Tim Shopen on Songhay stands out. IU Linguistics has also forwarded theoretical work on African languages, such as John Goldsmith’s seminal research on tone in African languages. The African linguistics faculty at IU have either founded or edited important journals in African Studies, African languages, and African linguistics, including Africa Today, Studies in African Linguistics, and Journal of African Languages and Linguistics. In 1972, the Indiana University Department of Linguistics hosted the Third Annual Conference of African Linguistics. Proceedings of that conference were published by Indiana University Publications (African Series, vol. 7). In 1986, IU hosted the Seventeenth Annual Conference of African Linguistics with Paul Newman and Robert Botne editing the proceedings in a volume entitled Current Approaches to African Linguistics, vol. 5. In 2016, Indiana University hosted the 48th Annual Conference on African Linguistics with the theme African Linguistics Across the Disciplines. Proceedings of that meeting are published in this volume. The papers presented in this volume reflect the diversity of opportunities for language study in Africa. This collection of descriptive and theoretical work is the fruit of data gathering both in-country and abroad by researchers of languages spoken across the continent, from Sereer-sin in the west to Somali in the northeast to Ikalanga in the south. The range of topics in this volume is also broad, representative of the varied field work in country and abroad that inspires research in African linguistics. This collection of papers spans the disciplines of phonology (both segmental and suprasegmental), morphology (both morphophonological and morphosyntactic), syntax, semantics, and language policy. The data and analyses presented in this volume offer a cross-disciplinary view of linguistic topics from the many under-resourced languages of Africa