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Dive into the research topics where Padmaja Paidipally is active.

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Featured researches published by Padmaja Paidipally.


Journal of Immunology | 2009

IL-22 Produced by Human NK Cells Inhibits Growth of Mycobacterium tuberculosis by Enhancing Phagolysosomal Fusion

Rohan Dhiman; Mohanalaxmi Indramohan; Peter F. Barnes; Ramesh C. Nayak; Padmaja Paidipally; L. Vijaya Mohan Rao; Ramakrishna Vankayalapati

We determined whether human NK cells could contribute to immune defenses against Mycobacterium tuberculosis through production of IL-22. CD3−CD56+ NK cells produced IL-22 when exposed to autologous monocytes and γ-irradiated M. tuberculosis, and this depended on the presence of IL-15 and IL-23, but not IL-12 or IL-18. IL-15-stimulated NK cells expressed 10.6 times more DAP10 mRNA compared with control NK cells, and DAP10 siRNA inhibited IL-15-mediated IL-22 production by NK cells. Soluble factors produced by IL-15-activated NK cells inhibited growth of M. tuberculosis in macrophages, and this effect was reversed by anti-IL-22. Addition of rIL-22 to infected macrophages enhanced phagolysosomal fusion and reduced growth of M. tuberculosis. We conclude that NK cells can contribute to immune defenses against M. tuberculosis through production of IL-22, which inhibits intracellular mycobacterial growth by enhancing phagolysosomal fusion. IL-15 and DAP-10 elicit IL-22 production by NK cells in response to M. tuberculosis.


The Journal of Infectious Diseases | 2011

Programmed Death 1 and Cytokine Inducible SH2-Containing Protein Dependent Expansion of Regulatory T Cells Upon Stimulation With Mycobacterium tuberculosis

Sivakumar Periasamy; Rohan Dhiman; Peter F. Barnes; Padmaja Paidipally; Amy R. Tvinnereim; Anuradha Bandaru; Vijaya Lakshmi Valluri; Ramakrishna Vankayalapati

We previously found that CD4(+)CD25(+)FoxP3(+) regulatory T cells (Tregs) expand in response to Mycobacterium tuberculosis infection in individuals who are healthy tuberculin reactors, but not in tuberculin-negative individuals. We also found that the M. tuberculosis mannose-capped lipoarabinomannan and prostaglandin E2 produced by monocytes are involved in Treg expansion. In this study, we found that Tregs expanded from CD4(+)CCR4(+) cells but not from CCR4(-) cells. However, introduction of CCR4 small interfering RNA (siRNA) into CD4(+) cells only marginally reduced expansion of Tregs. Using siRNA and neutralizing antibodies, we found that expansion of Tregs by M. tuberculosis required expression of programmed death1 (PD-1) and expression of the signaling molecule, cytokine inducible SH2-containing protein (CISH). Anti-PD-1 siRNA inhibited expression of CISH by expanded Tregs. M. tuberculosis-expanded Tregs produced transforming growth factor β and interleukin 10 and reduced the frequency of interferon γ-producing autologous CD8(+) cells. We conclude that M. tuberculosis infection induces development of Tregs from CCR4(+) cells through a process that depends on PD-1and CISH.


The Journal of Infectious Diseases | 2014

Interleukin 22 Inhibits Intracellular Growth of Mycobacterium tuberculosis by Enhancing Calgranulin A Expression

Rohan Dhiman; Sambasivan Venkatasubramanian; Padmaja Paidipally; Peter F. Barnes; Amy R. Tvinnereim; Ramakrishna Vankayalapati

Previously, we found that interleukin 22 (IL-22) inhibits intracellular growth of Mycobacterium tuberculosis in human monocyte-derived macrophages (MDMs). In the current study, we determined the mechanisms underlying these effects. We found that W7, a phagolysosomal fusion inhibitor, abrogates IL-22-dependent M. tuberculosis growth inhibition in MDMs, suggesting that IL-22 acts through enhanced phagolysosomal fusion. Our microarray analysis indicated that recombinant IL-22 (rIL-22) enhances the expression of an intracellular signaling molecule, calgranulin A. This was confirmed by real-time polymerase chain reaction, Western blot, and confocal microscopy. Calgranulin A small interfering RNA (siRNA) abrogated rIL-22-dependent growth inhibition of M. tuberculosis in MDMs. IL-22 enhanced Rab7 expression and downregulated Rab14 expression of M. tuberculosis-infected MDMs, and these effects were reversed by calgranulin A siRNA. These results suggest that M. tuberculosis growth inhibition by IL-22 depends on calgranulin A and enhanced phagolysosomal fusion, which is associated with increased Rab7 and reduced Rab14 expression.


Mucosal Immunology | 2017

IL-21-dependent expansion of memory-like NK cells enhances protective immune responses against Mycobacterium tuberculosis.

Sambasivan Venkatasubramanian; Satyanarayana Swamy Cheekatla; Padmaja Paidipally; Deepak Tripathi; Elwyn Welch; Amy Tvinnereim; Roza Nurieva; Ramakrishna Vankayalapati

Natural killer (NK) cells are traditionally considered as innate cells, but recent studies suggest that NK cells can distinguish antigens, and that memory NK cells expand and protect against viral pathogens. Limited information is available about the mechanisms involved in memory-like NK cell expansion, and their role in bacterial infections and vaccine-induced protective immune responses. In the current study, using a mouse model of tuberculosis (TB) infection, we found that interferon-gamma producing CD3−NKp46+CD27+KLRG1+ memory-like NK cells develop during Bacille Calmette–Guérin vaccination, expand, and provide protection against challenge with Mycobacterium tuberculosis (M. tb). Using antibodies, short interfering RNA and gene-deleted mice, we found that expansion of memory-like NK cells depends on interleukin 21 (IL-21). NKp46+CD27+KLRG1+ NK cells expanded in healthy individuals with latent TB infection in an IL-21-dependent manner. Our study provides first evidence that memory-like NK cells survive long term, expansion depends on IL-21, and involved in vaccine-induced protective immunity against a bacterial pathogen.


Journal of Immunology | 2009

NKG2D-Dependent IL-17 Production by Human T Cells in Response to an Intracellular Pathogen

Padmaja Paidipally; Sivakumar Periasamy; Peter F. Barnes; Rohan Dhiman; Mohanalaxini Indramohan; David E. Griffith; David Cosman; Ramakrishna Vankayalapati

We studied the factors that control IL-17 production in human Mycobacterium tuberculosis infection. CD4+ cells from healthy tuberculin reactors produced IL-17 in response to autologous M. tuberculosis-stimulated monocytes, and most IL-17+ cells were Ag experienced, CD4+CD62L−. IL-17 production by CD4+ cells was inhibited by anti-IL-23, but not by Abs to IL-1, IL-6, or TGF-β. Anti-NKG2D reduced IL-17 production and the frequency of CD4+CD62− IL-17+ cells, suggesting that NKG2D stimulates IL-17 production. CD4+NKG2D+ cells did not produce IL-17. Monocytes and alveolar macrophages from healthy donors produced IL-23 in response to M. tuberculosis. Addition of CD4+ cells markedly enhanced IL-23 production by M. tuberculosis-stimulated monocytes, and this was inhibited by anti-NKG2D and by Abs to UL-16 binding protein (ULB)1, a ligand for NKG2D on APCs. We conclude that binding of NKG2D to UL-16 binding protein (ULB)1 contributes to IL-23-dependent IL-17 production by CD4+ cells in human M. tuberculosis infection.


European Journal of Immunology | 2016

Tissue factor expression by myeloid cells contributes to protective immune response against Mycobacterium tuberculosis infection

Sambasivan Venkatasubramanian; Deepak Tripathi; Torry A. Tucker; Padmaja Paidipally; Satyanarayana Swamy Cheekatla; Elwyn Welch; Anjana Raghunath; Ann Jeffers; Amy Tvinnereim; Melissa E. Schechter; Bruno B. Andrade; Nizel Mackman; Steven Idell; Ramakrishna Vankayalapati

Tissue factor (TF) is a transmembrane glycoprotein that plays an essential role in hemostasis by activating coagulation. TF is also expressed by monocytes/macrophages as part of the innate immune response to infections. In the current study, we determined the role of TF expressed by myeloid cells during Mycobacterium tuberculosis (M. tb) infection by using mice lacking the TF gene in myeloid cells (TFΔ) and human monocyte derived macrophages (MDMs). We found that during M. tb infection, a deficiency of TF in myeloid cells was associated with reduced inducible nitric oxide synthase (iNOS) expression, enhanced arginase 1 (Arg1) expression, enhanced IL‐10 production and reduced apoptosis in infected macrophages, which augmented M. tb growth. Our results demonstrate that a deficiency of TF in myeloid cells promotes M2‐like phenotype in M .tb infected macrophages. A deficiency in TF expression by myeloid cells was also associated with reduced fibrin deposition and increased matrix metalloproteases (MMP)‐2 and MMP‐9 mediated inflammation in M. tb infected lungs. Our studies demonstrate that TF expressed by myeloid cells has newly recognized abilities to polarize macrophages and to regulate M. tb growth.


PLOS Pathogens | 2016

NK-CD11c+ Cell Crosstalk in Diabetes Enhances IL-6-Mediated Inflammation during Mycobacterium tuberculosis Infection

Satyanarayana Swamy Cheekatla; Deepak Tripathi; Sambasivan Venkatasubramanian; Pavan Kumar Nathella; Padmaja Paidipally; Munenori Ishibashi; Elwyn Welch; Amy Tvinnereim; Mitsuo Ikebe; Vijaya Lakshmi Valluri; Subash Babu; Hardy Kornfeld; Ramakrishna Vankayalapati

In this study, we developed a mouse model of type 2 diabetes mellitus (T2DM) using streptozotocin and nicotinamide and identified factors that increase susceptibility of T2DM mice to infection by Mycobacterium tuberculosis (Mtb). All Mtb-infected T2DM mice and 40% of uninfected T2DM mice died within 10 months, whereas all control mice survived. In Mtb-infected mice, T2DM increased the bacterial burden and pro- and anti-inflammatory cytokine and chemokine production in the lungs relative to those in uninfected T2DM mice and infected control mice. Levels of IL-6 also increased. Anti-IL-6 monoclonal antibody treatment of Mtb-infected acute- and chronic-T2DM mice increased survival (to 100%) and reduced pro- and anti-inflammatory cytokine expression. CD11c+ cells were the major source of IL-6 in Mtb-infected T2DM mice. Pulmonary natural killer (NK) cells in Mtb-infected T2DM mice further increased IL-6 production by autologous CD11c+ cells through their activating receptors. Anti-NK1.1 antibody treatment of Mtb-infected acute-T2DM mice increased survival and reduced pro- and anti-inflammatory cytokine expression. Furthermore, IL-6 increased inflammatory cytokine production by T lymphocytes in pulmonary tuberculosis patients with T2DM. Overall, the results suggest that NK-CD11c+ cell interactions increase IL-6 production, which in turn drives the pathological immune response and mortality associated with Mtb infection in diabetic mice.


Nature Communications | 2016

A TLR9 agonist promotes IL-22-dependent pancreatic islet allograft survival in type 1 diabetic mice

Deepak Tripathi; Sambasivan Venkatasubramanian; Satyanarayana Swamy Cheekatla; Padmaja Paidipally; Elwyn Welch; Amy R. Tvinnereim; Ramakrishna Vankayalapati

Pancreatic islet transplantation is a promising potential cure for type 1 diabetes (T1D). Islet allografts can survive long term in the liver parenchyma. Here we show that liver NK1.1+ cells induce allograft tolerance in a T1D mouse model. The tolerogenic effects of NK1.1+ cells are mediated through IL-22 production, which enhances allograft survival and increases insulin secretion. Increased expression of NKG2A by liver NK1.1+ cells in islet allograft-transplanted mice is involved in the production of IL-22 and in the reduced inflammatory response to allografts. Vaccination of T1D mice with a CpG oligonucleotide TLR9 agonist (ODN 1585) enhances expansion of IL-22-producing CD3-NK1.1+ cells in the liver and prolongs allograft survival. Our study identifies a role for liver NK1.1+ cells, IL-22 and CpG oligonucleotides in the induction of tolerance to islet allografts in the liver parenchyma.


Journal of Immunology | 2017

IL-21 Receptor Signaling Is Essential for Optimal CD4(+) T Cell Function and Control of Mycobacterium tuberculosis Infection in Mice.

Satyanarayana Swamy Cheekatla; Deepak Tripathi; Sambasivan Venkatasubramanian; Padmaja Paidipally; Elwyn Welch; Amy Tvinnereim; Roza Nurieva; Ramakrishna Vankayalapati

In this study, we determined the role of IL-21R signaling in Mycobacterium tuberculosis infection, using IL-21R knockout (KO) mice. A total of 50% of M. tuberculosis H37Rv–infected IL-21R KO mice died in 6 mo compared with no deaths in infected wild type (WT) mice. M. tuberculosis–infected IL-21R KO mice had enhanced bacterial burden and reduced infiltration of Ag-specific T cells in lungs compared with M. tuberculosis–infected WT mice. Ag-specific T cells from the lungs of M. tuberculosis–infected IL-21R KO mice had increased expression of T cell inhibitory receptors, reduced expression of chemokine receptors, proliferated less, and produced less IFN- γ, compared with Ag-specific T cells from the lungs of M. tuberculosis–infected WT mice. T cells from M. tuberculosis–infected IL-21R KO mice were unable to induce optimal macrophage responses to M. tuberculosis. This may be due to a decrease in the Ag-specific T cell population. We also found that IL-21R signaling is associated with reduced expression of a transcriptional factor Eomesodermin and enhanced functional capacity of Ag-specific T cells of M. tuberculosis–infected mice. The sum of our findings suggests that IL-21R signaling is essential for the optimal control of M. tuberculosis infection.


Scientific Reports | 2018

c-Jun N-terminal kinase 1 defective CD4+CD25+FoxP3+ cells prolong islet allograft survival in diabetic mice

Deepak Tripathi; Satyanarayana Swamy Cheekatla; Padmaja Paidipally; Rajesh Kumar Radhakrishnan; Elwyn Welch; Ramya Sivangala Thandi; Amy R. Tvinnereim; Ramakrishna Vankayalapati

CD4+CD25+FoxP3+ cells (Tregs) inhibit inflammatory immune responses to allografts. Here, we found that co-transplantation of allogeneic pancreatic islets with Tregs that are defective in c-Jun N-terminal kinase 1 (JNK1) signaling prolongs islet allograft survival in the liver parenchyma of chemically induced diabetic mice (CDM). Adoptively transferred JNK1−/− but not wild-type (WT) Tregs survive longer in the liver parenchyma of CDM. JNK1−/− Tregs are resistant to apoptosis and express anti-apoptotic molecules. JNK1−/− Tregs express higher levels of lymphocyte activation gene-3 molecule (LAG-3) on their surface and produce higher amounts of the anti-inflammatory cytokine interleukin (IL)-10 compared with WT Tregs. JNK1−/− Tregs inhibit liver alloimmune responses more efficiently than WT Tregs. JNK1−/− but not WT Tregs are able to inhibit IL-17 and IL-21 production through enhanced LAG-3 expression and IL-10 production. Our study identifies a novel role of JNK1 signaling in Tregs that enhances islet allograft survival in the liver parenchyma of CDM.

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Sambasivan Venkatasubramanian

University of Texas Health Science Center at Tyler

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Deepak Tripathi

University of Texas Health Science Center at Tyler

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Elwyn Welch

University of Texas Health Science Center at Tyler

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Satyanarayana Swamy Cheekatla

University of Texas Health Science Center at Tyler

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Rohan Dhiman

University of Texas Health Science Center at Tyler

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Amy Tvinnereim

University of Texas Health Science Center at Tyler

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Peter F. Barnes

University of Texas Health Science Center at Tyler

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Peter J. Barnes

National Institutes of Health

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