Publications

Recent Publications

1. McMaster Immunology Research Centre, Michael G. DeGroote Center for Learning and Discovery, McMaster University, Hamilton, ON L8S 4K1, Canada.

2. Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON L8S 4K1, Canada.

3. Department of Medical Biology, Laval University, Quebec City, QC G1V 0A6, Canada.

More than 40% of HIV infections occur via female reproductive tract (FRT) through heterosexual transmission. Epithelial cells that line the female genital mucosa are the first line of defense against HIV-1 and other sexually transmitted pathogens. These sentient cells recognize and respond to external stimuli by induction of a range of carefully balanced innate immune responses. Previously, we have shown that in response to HIV-1 gp120, the genital epithelial cells (GECs) from upper reproductive tract induce an inflammatory response that may facilitate HIV-1 translocation and infection. In this study, we report that the endometrial and endocervical GECs simultaneously induce biologically active interferon-β (IFNβ) antiviral responses following exposure to HIV-1 that act to protect the epithelial tight junction barrier. The innate antiviral response was directly induced by HIV-1 envelope glycoprotein gp120 and addition of gp120 neutralizing antibody inhibited IFNβ production. Interferon-β was induced by gp120 in upper GECs through Toll-like receptor 2 signaling and required presence of heparan sulfate on epithelial cell surface. The induction of IFNβ was dependent upon activation of transcription factor IRF3 (interferon regulatory factor 3). The IFNβ was biologically active, had a protective effect on epithelial tight junction barrier and was able to inhibit HIV-1 infection in TZM-bl indicator cells and HIV-1 replication in T cells. This is the first report that recognition of HIV-1 by upper GECs leads to induction of innate antiviral pathways. This could explain the overall low infectivity of HIV-1 in the FRT and could be exploited for HIV-1 prophylaxis.Cellular and Molecular Immunology advance online publication, 19 March 2018; doi:10.1038/cmi.2017.168.

Transcriptional profiling of primary endometrial epithelial cells following acute HIV-1 exposure reveals gene signatures related to innate immunity.

Zahoor MA, Woods MW, Dizzell S, Nazli A, Mueller KM, Nguyen PV, Verschoor CP, Kaushic C.

Am J Reprod Immunol. 2018 Feb 8. doi: 10.1111/aji.12822. [Epub ahead of print]

1. McMaster Immunology Research Centre, M.G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario L8S 4K1, Canada; and Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario L8S 4K1, Canada.

2. McMaster Immunology Research Centre, M.G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario L8S 4K1, Canada; and Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario L8S 4K1, Canada xingz@mcmaster.ca.

Mycobacterium tuberculosis, the pathogen causing pulmonary tuberculosis (TB) in humans, has evolved to delay Th1 immunity in the lung. Although conventional dendritic cells (cDCs) are known to be critical to the initiation of T cell immunity, the differential roles and molecular mechanisms of migratory CD11b+ and CD103+ cDC subsets in anti-M. tuberculosis Th1 activation remain unclear. Using a murine model of pulmonary M. tuberculosis infection, we found that slow arrival of M. tuberculosis-bearing migratory CD11b+ and CD103+ cDCs at the draining lymph nodes preceded the much-delayed Th1 immunity and protection in the lung. Contrary to their previously described general roles in Th polarization, CD11b+ cDCs, but not CD103+ cDCs, were critically required for Th1 activation in draining lymph nodes following M. tuberculosis infection. CD103+ cDCs counterregulated CD11b+ cDC-mediated Th1 activation directly by producing the immune-suppressive cytokine IL-10. Thus, our study provides new mechanistic insights into differential Th immune regulation by migratory cDC subsets and helps to develop novel vaccines and therapies.

Hormonal Contraception and HIV-1 Acquisition: Biological Mechanisms

Hapgood JP, Kaushic C, Hel Z.

Endocr Rev. 2018 Jan 4. doi: 10.1210/er.2017-00103.

Frequency of Human CD45+ Target Cells is a Key Determinant of Intravaginal HIV-1 Infection in Humanized Mice

Philip V. Nguyen, Jocelyn M. Wessels, Kristen Mueller, Fatemeh Vahedi, Varun Anipindi, Chris P. Verschoor, Marianne Chew, Alexandre Deshiere, Uladzimir Karniychuk, Tony Mazzulli, Michel J. Tremblay, Ali A. Ashkar & Charu Kaushic

Scientific Reports 7, Article number: 15263(2017) doi:10.1038/s41598-017-15630-z

Medroxyprogesterone acetate-treated human, primary endometrial epithelial cells reveal unique gene expression signature linked to innate immunity and HIV-1 susceptibility.

Woods MW, Zahoor MA, Dizzell S, Verschoor CP, Kaushic C

Am J Reprod Immunol. 2017 Nov 6. doi: 10.1111/aji.12781. 

Association of high-risk sexual behaviour with diversity of the vaginal microbiota and abundance of Lactobacillus.

Wessels JM, Lajoie J, Vitali D, Omollo K, Kimani J, Oyugi J, Cheruiyot J, Kimani M, Mungai JN, Akolo M, Stearns JC, Surette MG, Fowke KR, Kaushic C

PLoS One. 2017 Nov 2;12(11):e0187612. doi: 10.1371/journal.pone.0187612. eCollection 2017.

A novel role for IL-17 in enhancing type 1 helper T cell immunity in the female genital tract following mucosal HSV-2 vaccination.

Bagri P, Anipindi VC, Nguyen PV, Vitali D, Stämpfli MR, Kaushic C.

J Virol. 2017 Sep 27. pii: JVI.01234-17. doi: 10.1128/JVI.01234-17. [Epub ahead of print]

Role of sex hormones and the vaginal microbiome in susceptibility and mucosal immunity to HIV-1 in the female genital tract.

Vitali D, Wessels JM, Kaushic C.

AIDS Res Ther. 2017 Sep 12;14(1):39. doi: 10.1186/s12981-017-0169-4.

Lee Y, Dizzell SE, Leung V, Zahoor MA, Fichorova RN, Kaushic C. 

Viruses. 2016 Aug 30;8(9). pii: E241. doi: 10.3390/v8090241.

PMID:27589787

Fangming Xiu, Varun C. Anipindi, Philip V. Nguyen, Jeanette Boudreau, Hong Liang, Yonghong Wan, Denis P. Snider, Charu Kaushic

PLoS One. 2016 April 11;11(4).:e0153304. doi: 10.1371/journal.pone.0153304.

PMID: 27064901

Anipindi VC, Bagri P, Roth K, Dizzell SE, Nguyen PV, Shaler CR, Chu DK, Jiménez-Saiz R, Liang H, Swift S, Nazli A, Kafka JK, Bramson J, Xing Z,Jordana M, Wan Y, Snider DP, Stampfli MR, Kaushic C.

PLoS Pathog. 2016 May 5;12(5):e1005589

PMID:27148737

Ferreira VH, Nazli A, Dizzell SE, Mueller K, Kaushic C

PLoS One. 2015 Apr 9;10(4):e0124903.
PMID: 25856395

Ferreira VH, Dizzell S, Nazli A, Kafka JK, Mueller K, Nguyen PV, Tremblay MJ, Cochrane A, Kaushic C

J Infect Dis. 2015 Jun 1;211(11):1745-56.
PMID: 25538276

Kafka JK, Osborne BJ, Sheth PM, Nazli A, Dizzell S, Huibner S, Kovacs C, Verschoor CP, Bowdish DM, Kaul R, Kaushic C.

Am J Reprod Immunol. 2015 Feb;73(2):151-61.
PMID: 25052241

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