Blood monocyte and dendritic cell profiles among people living with HIV with Mycobacterium tuberculosis co-infection

Abstract Background Understanding the complex interactions of the immune response mediated by Mycobacterium tuberculosis and HIV co-infection is fundamental to disease biomarker discovery, vaccine, and drug development. Using flow cytometry, we characterized the frequencies and phenotypic difference...

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Main Authors: Santhuri Rambaran, Thando Glory Maseko, Lara Lewis, Razia Hassan-Moosa, Derseree Archary, Sinaye Ngcapu, Nigel Garrett, Lyle R. McKinnon, Nesri Padayatchi, Kogieleum Naidoo, Aida Sivro
Format: Article
Language:English
Published: BMC 2023-07-01
Series:BMC Immunology
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Online Access:https://doi.org/10.1186/s12865-023-00558-z
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author Santhuri Rambaran
Thando Glory Maseko
Lara Lewis
Razia Hassan-Moosa
Derseree Archary
Sinaye Ngcapu
Nigel Garrett
Lyle R. McKinnon
Nesri Padayatchi
Kogieleum Naidoo
Aida Sivro
author_facet Santhuri Rambaran
Thando Glory Maseko
Lara Lewis
Razia Hassan-Moosa
Derseree Archary
Sinaye Ngcapu
Nigel Garrett
Lyle R. McKinnon
Nesri Padayatchi
Kogieleum Naidoo
Aida Sivro
author_sort Santhuri Rambaran
collection DOAJ
description Abstract Background Understanding the complex interactions of the immune response mediated by Mycobacterium tuberculosis and HIV co-infection is fundamental to disease biomarker discovery, vaccine, and drug development. Using flow cytometry, we characterized the frequencies and phenotypic differences in monocytes and dendritic cell populations using peripheral blood mononuclear cells from individuals with recurrent, active pulmonary tuberculosis with and without coexisting HIV infection (CAPRISA 011, Clinicaltrials.gov, NCT02114684, 29/01/2014) and compared them to samples from HIV positive individuals and healthy controls. Additionally, we assessed the associations between the frequency of monocyte and dendritic cell subsets and time to culture conversion and cavitary disease in patients with active TB using a cox proportional hazards and logistic regression models. Results Compared to healthy controls, the frequency of total monocytes (HLA-DR + CD14 +) was significantly higher in the TB/HIV and TB groups and the frequency of dendritic cells (HLA-DR + CD14-) was significantly higher in TB/HIV and HIV groups. We observed significant variation in the expression of CCR2, CD40, CD11b, CD86, CD163, CX3CR1 across different cell subsets in the four study groups. Increase in CCR2, CD11b and CD40 was associated with active TB infection, while decrease in CX3CR1 and increase in CD163 was associated with HIV infection. Expression of CX3CR1 (aHR 0.98, 95% CI 0.963 – 0.997, p = 0.019) on non-classical monocytes associated with longer time to TB culture conversion in the multivariable model correcting for randomization arm, age, sex, HIV status, lung cavitation, alcohol use, smoking and BMI. Higher surface expression of CD86 (aOR 1.017, 95% CI 1.001 – 1.032, p = 0.033) on intermediate monocytes associated with the presence of lung cavitation, while higher expression of transitional monocytes (aOR 0.944, 95% CI 0.892 – 0.999, p = 0.047) associated with the absence of lung cavitation in the multivariable model. Conclusion These data provide valuable insight into the heterogenous role of monocyte and dendritic cells in TB and HIV infections.
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spelling doaj.art-a658362593444ca1815068ef3d1a045a2023-07-23T11:10:30ZengBMCBMC Immunology1471-21722023-07-0124111110.1186/s12865-023-00558-zBlood monocyte and dendritic cell profiles among people living with HIV with Mycobacterium tuberculosis co-infectionSanthuri Rambaran0Thando Glory Maseko1Lara Lewis2Razia Hassan-Moosa3Derseree Archary4Sinaye Ngcapu5Nigel Garrett6Lyle R. McKinnon7Nesri Padayatchi8Kogieleum Naidoo9Aida Sivro10Centre for the AIDS Programme of Research in South Africa (CAPRISA)Centre for the AIDS Programme of Research in South Africa (CAPRISA)Centre for the AIDS Programme of Research in South Africa (CAPRISA)Centre for the AIDS Programme of Research in South Africa (CAPRISA)Centre for the AIDS Programme of Research in South Africa (CAPRISA)Centre for the AIDS Programme of Research in South Africa (CAPRISA)Centre for the AIDS Programme of Research in South Africa (CAPRISA)Centre for the AIDS Programme of Research in South Africa (CAPRISA)Centre for the AIDS Programme of Research in South Africa (CAPRISA)Centre for the AIDS Programme of Research in South Africa (CAPRISA)Centre for the AIDS Programme of Research in South Africa (CAPRISA)Abstract Background Understanding the complex interactions of the immune response mediated by Mycobacterium tuberculosis and HIV co-infection is fundamental to disease biomarker discovery, vaccine, and drug development. Using flow cytometry, we characterized the frequencies and phenotypic differences in monocytes and dendritic cell populations using peripheral blood mononuclear cells from individuals with recurrent, active pulmonary tuberculosis with and without coexisting HIV infection (CAPRISA 011, Clinicaltrials.gov, NCT02114684, 29/01/2014) and compared them to samples from HIV positive individuals and healthy controls. Additionally, we assessed the associations between the frequency of monocyte and dendritic cell subsets and time to culture conversion and cavitary disease in patients with active TB using a cox proportional hazards and logistic regression models. Results Compared to healthy controls, the frequency of total monocytes (HLA-DR + CD14 +) was significantly higher in the TB/HIV and TB groups and the frequency of dendritic cells (HLA-DR + CD14-) was significantly higher in TB/HIV and HIV groups. We observed significant variation in the expression of CCR2, CD40, CD11b, CD86, CD163, CX3CR1 across different cell subsets in the four study groups. Increase in CCR2, CD11b and CD40 was associated with active TB infection, while decrease in CX3CR1 and increase in CD163 was associated with HIV infection. Expression of CX3CR1 (aHR 0.98, 95% CI 0.963 – 0.997, p = 0.019) on non-classical monocytes associated with longer time to TB culture conversion in the multivariable model correcting for randomization arm, age, sex, HIV status, lung cavitation, alcohol use, smoking and BMI. Higher surface expression of CD86 (aOR 1.017, 95% CI 1.001 – 1.032, p = 0.033) on intermediate monocytes associated with the presence of lung cavitation, while higher expression of transitional monocytes (aOR 0.944, 95% CI 0.892 – 0.999, p = 0.047) associated with the absence of lung cavitation in the multivariable model. Conclusion These data provide valuable insight into the heterogenous role of monocyte and dendritic cells in TB and HIV infections.https://doi.org/10.1186/s12865-023-00558-zPulmonary-tuberculosisInflammationHIVMonocytesDendritic cells
spellingShingle Santhuri Rambaran
Thando Glory Maseko
Lara Lewis
Razia Hassan-Moosa
Derseree Archary
Sinaye Ngcapu
Nigel Garrett
Lyle R. McKinnon
Nesri Padayatchi
Kogieleum Naidoo
Aida Sivro
Blood monocyte and dendritic cell profiles among people living with HIV with Mycobacterium tuberculosis co-infection
BMC Immunology
Pulmonary-tuberculosis
Inflammation
HIV
Monocytes
Dendritic cells
title Blood monocyte and dendritic cell profiles among people living with HIV with Mycobacterium tuberculosis co-infection
title_full Blood monocyte and dendritic cell profiles among people living with HIV with Mycobacterium tuberculosis co-infection
title_fullStr Blood monocyte and dendritic cell profiles among people living with HIV with Mycobacterium tuberculosis co-infection
title_full_unstemmed Blood monocyte and dendritic cell profiles among people living with HIV with Mycobacterium tuberculosis co-infection
title_short Blood monocyte and dendritic cell profiles among people living with HIV with Mycobacterium tuberculosis co-infection
title_sort blood monocyte and dendritic cell profiles among people living with hiv with mycobacterium tuberculosis co infection
topic Pulmonary-tuberculosis
Inflammation
HIV
Monocytes
Dendritic cells
url https://doi.org/10.1186/s12865-023-00558-z
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