Cell Host Research Articles

Dendritic cell expression of CD24 contributes to optimal priming of T lymphocytes in lymph nodes.

CD24 is a GPI anchored cell surface glycoprotein whose function as a co-stimulatory molecule has been implicated. However, the function of CD24 on antigen presenting cells during T cell responses is not well understood. Here we show that in the CD24-deficient host, adoptively transferred CD4+ T cells undergo inefficient expansion and have accelerated cell death in lymph nodes, which results in insufficient priming of T cells. Insufficient expansion of T cells in the CD24-deficient host was not due to host anti-CD24 response by NK, T and B lymphocytes. Transgenic expression of CD24 on DC in CD24-/- mice restored T cell accumulation and survival in draining lymph nodes. Consistent with these findings, MHC II tetramer staining also revealed that an antigen-specific polyclonal T cell response was reduced in lymph nodes of CD24-/- mice. Taken together, we have revealed a novel role of CD24 on DC in optimal T cell priming in lymph nodes. These data suggest that CD24 blockade should lower unwanted T cell responses such as those in autoimmune diseases.

Comparative transcriptomics from intestinal cells of permissive and non-permissive hosts during Ancylostoma ceylanicum infection reveals unique signatures of protection and host specificity.

Soil-transmitted nematodes (STNs) place a tremendous burden on health and economics worldwide with an estimate of at least 1.5 billion people, or 24% of the population, being infected with at least 1 STN globally. Children and pregnant women carry the heavier pathological burden, and disease caused by the blood-feeding worm in the intestine can result in anaemia and delays in physical and intellectual development. These parasites are capable of infecting and reproducing in various host species, but what determines host specificity remains unanswered. Identifying the molecular determinants of host specificity would provide a crucial breakthrough towards understanding the biology of parasitism and could provide attractive targets for intervention. To investigate specificity mechanisms, members of the hookworm genus Ancylostoma provide a powerful system as they range from strict specialists to generalists. Using transcriptomics, differentially expressed genes (DEGs) in permissive (hamster) and non-permissive (mouse) hosts at different early time points during infection with A. ceylanicum were examined. Analysis of the data has identified unique immune responses in mice, as well as potential permissive signals in hamsters. Specifically, immune pathways associated with resistance to infection are upregulated in the non-permissive host, providing a possible protection mechanism that is absent in the permissive host. Furthermore, unique signatures of host specificity that may inform the parasite that it has invaded a permissive host were identified. These data provide novel insight into the tissue-specific gene expression differences between permissive and non-permissive hosts in response to hookworm infection.

Cryo-Electron Tomography: The Resolution Revolution and a Surge of In Situ Virological Discoveries.

The recent proliferation of cryo-electron tomography (cryo-ET) techniques has led to the cryo-ET resolution revolution. Meanwhile, significant efforts have been made to improve the identification of targets in the cellular context and the throughput of cryo-focused ion beam (FIB) milling. Together, these developments led to a surge of in situ discoveries on how enveloped viruses are assembled and how viruses interact with cells in infected hosts. In this article, we review the recent advances in cryo-ET, high-resolution insights into virus assembly, and the findings from inside infected eukaryotic and prokaryotic cells.

Exposing and exploiting host-parasite arms race clues in SARS-CoV-2: a principally new method for improved T cell immunogenicity prediction.

Computational prediction of T cell epitopes is a crucial component in the development of novel vaccines. T cells in a healthy vertebrate host can recognize as non-self only those peptides that are present in the parasite's proteins but absent in the host's proteins. This principle enables us to determine the current and past host specificity of a parasite and to predict peptides capable of eliciting a T cell response. Building upon the detailed mapping of T cell clone specificity for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) antigens, we employed Monte Carlo tests to determine that empirically confirmed T cell-stimulating peptides have a significantly increased proportion of pentapeptides, hexapeptides and heptapeptides not found in the human proteome (P < 0.0001, Cohen's d > 4.9). We observed a lower density of potential pentapeptide targets for T cell recognition in the spike protein from the human-adapted SARS-CoV-2 ancestor compared to 10 other SARS-CoV-2 proteins originating from the horseshoe bat-adapted ancestor. Our novel method for predicting T cell immunogenicity of SARS-CoV-2 peptides is four times more effective than previous approaches. We recommend utilizing our theory-based method where efficient empirically based algorithms are unavailable, such as in the development of certain veterinary vaccines, and combining it with empirical methods in other cases for optimal results.

Tumor Growth Remains Refractory to Myc Ablation in Host Macrophages.

Aberrant expression of the oncoprotein c-Myc (Myc) is frequently observed in solid tumors and is associated with reduced overall survival. In addition to well-recognized cancer cell-intrinsic roles of Myc, studies have also suggested tumor-promoting roles for Myc in cells of the tumor microenvironment, including macrophages and other myeloid cells. Here, we benchmark Myc inactivation in tumor cells against the contribution of its expression in myeloid cells of murine hosts that harbor endogenous or allograft tumors. Surprisingly, we observe that LysMCre-mediated Myc ablation in host macrophages does not attenuate tumor growth regardless of immunogenicity, the cellular origin of the tumor, the site it develops, or the stage along the tumor progression cascade. Likewise, we find no evidence for Myc ablation to revert or antagonize the polarization of alternatively activated immunosuppressive macrophages. Thus, we surmise that systemic targeting of Myc activity may confer therapeutic benefits primarily through limiting Myc activity in tumor cells rather than reinvigorating the anti-tumor activity of macrophages.

Assessing the effects of Leishmania (Leishmania) infantum and L. (L.) amazonensis infections in macrophages using a quantitative proteome approach

Leishmania (Leishmania) infantum is the causative agent of visceral leishmaniasis, while L. (L.) amazonensis is associated with localized cutaneous and diffuse leishmaniasis, which can affect different organ tissues leading to visceral manifestations in some hosts. The wide range of clinical manifestations of leishmaniasis depends on host factors such as the immune response and on the species of Leishmania involved in the infection. Macrophages are the main infected cells in the vertebrate host, and proteins play a pivotal role in Leishmania-macrophage interactions. Here, we performed difference gel electrophoresis (DIGE) and shotgun quantitative mass spectrometry-based proteomics by means of tandem mass tags (TMT) isobaric peptide labeling followed by LC-MS/MS to investigate differentially abundant proteins in BALB/c macrophages infected with these Leishmania species. Using DIGE for comparison, we found that 2.34% spots (29/1240) were differentially intense in infected murine macrophages. Leishmania (L.) infantum and L. (L.) amazonensis induced similar changes in the host cells; 11 spots were selected as differentially intense in each species and seven in the uninfected control group. Using TMT, 5939 Mus musculus proteins were identified, of which 410 and 433 were differentially abundant in L. (L.) infantum and L. (L.) amazonensis infections, respectively, while 170 proteins were commonly regulated by both the species. Gene ontology enrichment analysis indicated that Leishmania infection interfered with apoptotic mechanisms in macrophages and induced epigenetic changes that may affect gene transcription. Moreover, downregulation of proteins such as PYCARD and MyD88 seemed to influence the inflammatory process in L. (L.) amazonensis infection, whereas upregulation of TAP1 and ERAP1 was involved in the adaptive immune response in L. (L.) infantum infection. Differentially abundant proteins identified in this study may contribute to a better understanding of the factors that determine the course of infection. Our results suggest several possible targets for vaccines, drugs, and diagnosis of leishmaniasis.

Research Highlights

Research Highlights

Transcriptome analysis reveals pathogenesis-related gene 1 pathway against salicylic acid treatment in grapevine (Vitis vinifera L).

Salicylic acid (SA) is a well-studied phenolic plant hormone that plays an important role in plant defense against the hemi-biothrophic and biothrophic pathogens and depends on the living cells of host for the successful infection. In this study, a pathogenesis test was performed between Vitis davidii and V. vinifera cultivars against grape white rot disease (Coniella diplodiella). V. davidii was found to be resistant against this disease. SA contents were found to be higher in the resistant grape cultivar after different time points. RNA-seq analysis was conducted on susceptible grapevine cultivars after 12, 24, and 48h of SA application with the hypothesis that SA may induce defense genes in susceptible cultivars. A total of 511 differentially expressed genes (DEGs) were identified from the RNA-seq data, including some important genes, VvWRKY1/2, VvNPR1, VvTGA2, and VvPR1, for the SA defense pathway. DEGs related to phytohormone signal transduction and flavonoid biosynthetic pathways were also upregulated. The quantitative real-time PCR (qRT-PCR) results of the significantly expressed transcripts were found to be consistent with the transcriptome data, with a high correlation between the two analyses. The pathogenesis-related gene 1 (VvPR1), which is an important marker gene for plant defense, was selected for further promoter analysis. The promoter sequence showed that it contains some important cis-elements (W-box, LS7, as-1, and TCA-element) to recruit the transcription factors VvWRKY, VvNPR1, and VvTGA2 to express the VvPR1 gene in response to SA treatment. Furthermore, the VvPR1 promoter was serially deleted into different fragments (-1,837, -1,443, -1,119, -864, -558, -436, and -192 ) bp and constructed vectors with the GUS reporter gene. Deletion analysis revealed that the VvPR1 promoter between -1837bp to -558bp induced significant GUS expression with respect to the control. On the basis of these results, the -558bp region was assumed to be an important part of the VvPR1 promoter, and this region contained the important cis-elements related to SA, such as TCA-element (-1,472bp), LS7 (-1,428 bp), and as-1 (-520bp), that recruit the TFs and induce the expression of the VvPR1 gene. This study expanded the available information regarding SA-induced defense in susceptible grapes and recognized the molecular mechanisms through which this defense might be mediated.

Peranan Sel Sistem Imun Alamiah Pada Infeksi Mycobacterium tuberculosis

Mycobacterium tuberculosis infection which causes tuberculosis is still a major health problem worldwide due to high morbidity and mortality, where in 2018 tuberculosis caused 1.5 million deaths. The degree of pulmonary tuberculosis varies from mild infiltration, chronic infection, cavity formation to severe and destructive tuberculosis. The difference in the degree of pulmonary tuberculosis is influenced by the response of the immune system to M. tuberculosis. When M. tuberculosis infects the lungs, the human immune system will carry out a series of processes to limit the spread and replication of bacteria. The immune system against M. tuberculosis consists of an innate immune system involving cellular components such as macrophages, neutrophils, Natural Killer (NK cells), dendritic cells and upper respiratory epithelium and an acquired immune response which is mainly mediated by T lymphocyte cells of host that is responsible for recognizing and controlling invasion by pathogens. This review will describe the role of natural immune system cells in M. tuberculosis infection. In addition, a complete description of M. tuberculosis infection will also be discussed to increase understanding of the role of natural immune system cells in M. tuberculosis infection.

Diverse susceptibilities and responses of human and rodent cells to orthohantavirus infection reveal different levels of cellular restriction.

Orthohantaviruses are rodent-borne emerging viruses that may cause severe diseases in humans but no apparent pathology in their small mammal reservoirs. However, the mechanisms leading to tolerance or pathogenicity in humans and persistence in rodent reservoirs are poorly understood, as is the manner in which they spread within and between organisms. Here, we used a range of cellular and molecular approaches to investigate the interactions of three different orthohantaviruses–Puumala virus (PUUV), responsible for a mild to moderate form of hemorrhagic fever with renal syndrome in humans, Tula virus (TULV) with low pathogenicity, and non-pathogenic Prospect Hill virus (PHV)–with human and rodent host cell lines. Besides the fact that cell susceptibility to virus infection was shown to depend on the cell type and virus strain, the three orthohantaviruses were able to infect Vero E6 and HuH7 human cells, but only the former secreted infectious particles. In cells derived from PUUV reservoir, the bank vole (Myodes glareolus), PUUV achieved a complete viral cycle, while TULV did not enter the cells and PHV infected them but did not produce infectious particles, reflecting differences in host specificity. A search for mature virions by electron microscopy (EM) revealed that TULV assembly occurred in part at the plasma membrane, whereas PHV particles were trapped in autophagic vacuoles in cells of the heterologous rodent host. We described differential interactions of orthohantaviruses with cellular factors, as supported by the cellular distribution of viral nucleocapsid protein with cell compartments, and proteomics identification of cellular partners. Our results also showed that interferon (IFN) dependent gene expression was regulated in a cell and virus species dependent manner. Overall, our study highlighted the complexity of the host-virus relationship and demonstrated that orthohantaviruses are restricted at different levels of the viral cycle. In addition, the study opens new avenues to further investigate how these viruses differ in their interactions with cells to evade innate immunity and how it depends on tissue type and host species.

Comparative single-cell transcriptional atlases of Babesia species reveal conserved and species-specific expression profiles.

Babesia is a genus of apicomplexan parasites that infect red blood cells in vertebrate hosts. Pathology occurs during rapid replication cycles in the asexual blood stage of infection. Current knowledge of Babesia replication cycle progression and regulation is limited and relies mostly on comparative studies with related parasites. Due to limitations in synchronizing Babesia parasites, fine-scale time-course transcriptomic resources are not readily available. Single-cell transcriptomics provides a powerful unbiased alternative for profiling asynchronous cell populations. Here, we applied single-cell RNA sequencing to 3 Babesia species (B. divergens, B. bovis, and B. bigemina). We used analytical approaches and algorithms to map the replication cycle and construct pseudo-synchronized time-course gene expression profiles. We identify clusters of co-expressed genes showing “just-in-time” expression profiles, with gradually cascading peaks throughout asexual development. Moreover, clustering analysis of reconstructed gene curves reveals coordinated timing of peak expression in epigenetic markers and transcription factors. Using a regularized Gaussian graphical model, we reconstructed co-expression networks and identified conserved and species-specific nodes. Motif analysis of a co-expression interactome of AP2 transcription factors identified specific motifs previously reported to play a role in DNA replication in Plasmodium species. Finally, we present an interactive web application to visualize and interactively explore the datasets.

SARS-CoV-2-neutralising monoclonal antibodies to prevent COVID-19.

SARS-CoV-2-neutralising monoclonal antibodies to prevent COVID-19.

Toll-like receptor 2 promotes breast cancer progression and resistance to chemotherapy

ABSTRACT Cancer stem cells (CSCs) are the main drivers of disease progression and chemotherapy resistance in breast cancer. Tumor progression and chemoresistance might then be prevented by CSC-targeted therapies. We previously demonstrated that Toll-like Receptor (TLR)2 is overexpressed in CSCs and fuels their self-renewal. Here, we show that high TLR2 expression is linked to poor prognosis in breast cancer patients, therefore representing a candidate target for breast cancer treatment. By using a novel mammary cancer-prone TLR2KO mouse model, we demonstrate that TLR2 is required for CSC pool maintenance and for regulatory T cell induction. Accordingly, cancer-prone TLR2KO mice display delayed tumor onset and increased survival. Transplantation of TLR2WT and TLR2KO cancer cells in either TLR2WT or TLR2KO hosts shows that tumor initiation is mostly sustained by TLR2 expression in cancer cells. TLR2 host deficiency partially impairs cancer cell growth, implying a pro-tumorigenic effect of TLR2 expression in immune cells. Finally, we demonstrate that doxorubicin-induced release of HMGB1 activates TLR2 signaling in cancer cells, leading to a chemotherapy-resistant phenotype. Unprecedented use of TLR2 inhibitors in vivo reduces tumor growth and potentiates doxorubicin efficacy with no negative impact on the host immune system, opening new perspectives for the treatment of breast cancer patients.

Characterization of Leishmania (L.) amazonensis oligopeptidase B and its role in macrophage infection.

Leishmania spp. are parasitic protozoa that cause leishmaniasis, a disease endemic in 98 countries. Leishmania promastigotes are transmitted by the vector and differentiate into amastigotes within phagocytic cells of the vertebrate host. To survive in multiple and hostile environments, the parasite has several virulence factors. Oligopeptidase B (OPB) is a serine peptidase present in prokaryotes, some eukaryotes and some higher plants. It has been considered a virulence factor in trypanosomatids, but only a few studies, performed with Old World species, analysed its role in Leishmania virulence or infectivity.L. (L.) amazonensis is an important agent of cutaneous leishmaniasis in Brazil. The L. (L.) amazonensis OPB encoding gene has been sequenced and analysed in silico but has never been expressed. In this work, we produced recombinant L. (L.) amazonensis OPB and showed that its pH preferences, Km and inhibition patterns are similar to those reported for L. (L.) major and L. (L.) donovani OPBs. Since Leishmania is known to secrete OPB, we performed in vitro infection assays using the recombinant enzyme. Our results showed that active OPB increased in vitro infection by L. (L.) amazonensis when present before and throughout infection. Our findings suggest that OPB is relevant to L. (L.) amazonensis infection, and that potential drugs acting through OPB will probably be effective for Old and New World Leishmania species. OPB inhibitors may eventually be explored for leishmaniasis chemotherapy.

Host cell proteins modulated upon Toxoplasma infection identified using proteomic approaches: a molecular rationale.

Toxoplasma gondii is a pathogenic protozoan parasite belonging to the apicomplexan phylum that infects the nucleated cells of warm-blooded hosts leading to an infectious disease known as toxoplasmosis. Apicomplexan parasites such as T. gondii can display different mechanisms to control or manipulate host cells signaling at different levels altering the host subcellular genome and proteome. Indeed, Toxoplasma is able to modulate host cell responses (especially immune responses) during infection to its advantage through both structural and functional changes in the proteome of different infected cells. Consequently, parasites can transform the invaded cells into a suitable environment for its own replication and the induction of infection. Proteomics as an applicable tool can identify such critical proteins involved in pathogen (Toxoplasma)-host cell interactions and consequently clarify the cellular mechanisms that facilitate the entry of pathogens into host cells, and their replication and transmission, as well as the central mechanisms of host defense against pathogens. Accordingly, the current paper reviews several proteins (identified using proteomic approaches) differentially expressed in the proteome of Toxoplasma-infected host cells (macrophages and human foreskin fibroblasts) and tissues (brain and liver) and highlights their plausible functions in the cellular biology of the infected cells. The identification of such modulated proteins and their related cell impact (cell responses/signaling) can provide further information regarding parasite pathogenesis and biology that might lead to a better understanding of therapeutic strategies and novel drug targets.

CD8+ T cell impairment drives severe human metapneumovirus respiratory disease in aged mice.

Abstract Objective Human metapneumovirus (HMPV) is a leading cause of severe respiratory disease in children &amp;lt;5, adults &amp;gt;65, and the immunocompromised. CD8+ T lymphocytes are the primary cell responsible for clearing HMPV infection in the lung. We tested the hypothesis that CD8+ T cell impairment in the aged host drives severe respiratory infection and delayed viral clearance. Methods B6 aged 72–73wk mice and young 6–7wk mice were infected with 2×106 PFU HMPV. Seven days post infection, mice were euthanized and lung, bronchoalveolar lavage (BAL), spleen, and draining lymph nodes were collected for flow cytometry. Lung and BAL supernatant was collected for viral titer, histology, and cytokine measurement. Results Aged mice lost more weight, had delayed viral clearance, and increased clinical scores and lung histopathology. Aged mice produced fewer HMPV-tetramer+ cells in lung and BAL. Aged CD8+ T lymphocytes in BAL co-expressed inhibitory receptors PD-1, TIM-3, LAG-3, and 2B4. Aged CD8+ T lymphocytes also upregulated senescence markers, T-bet and EOMES. Upon ex vivo peptide stimulation, aged CD8+ T cells produced significantly less granzyme B compared to young CD8+ T cells. Adoptive transfer of young T cells into aged mice rescued this severe disease phenotype. Young CD8+ cells in the aged host produced more tetramer+ cells and granzyme B and had less senescent marker expression. Conclusion Aged mice exhibit more severe respiratory disease when infected with HMPV. Aged CD8+ T cells appear to be impaired and upregulate senescence markers that contribute to severe HMPV infection in the aged host. Supported by: NIH/NIAID 5R01 AI085062-09, John V. Williams, MD NIH T32GM008208 Medical Scientist Training Program, University of Pittsburgh School of Medicine

Mining the Proteome of Toxoplasma Parasites Seeking Vaccine and Diagnostic Candidates.

Simple SummaryThe One Health concept to toxoplasmosis highlights that the health of humans is closely related to the health of animals and our common environment. Toxoplasmosis outcomes might be severe and fatal in patients with immunodeficiency, diabetes, and pregnant women and infants. Consequently, the development of effective vaccine and diagnostic strategies is urgent for the elimination of this disease. Proteomics analysis has allowed the identification of key proteins that can be utilized in the development of novel disease diagnostics and vaccines. This work presents relevant proteins found in the proteome of the life cycle-specific stages of Toxoplasma parasites. In fact, it brings together the main functionality key proteins from Toxoplasma parasites coming from proteomic approaches that are most likely to be useful in improving the disease management, and critically proposes innovative directions to finally develop promising vaccines and diagnostics tools.Toxoplasma gondii is a pathogenic protozoan parasite that infects the nucleated cells of warm-blooded hosts leading to an infectious zoonotic disease known as toxoplasmosis. The infection outcomes might be severe and fatal in patients with immunodeficiency, diabetes, and pregnant women and infants. The One Health approach to toxoplasmosis highlights that the health of humans is closely related to the health of animals and our common environment. The presence of drug resistance and side effects, the further improvement of sensitivity and specificity of serodiagnostic tools and the potentiality of vaccine candidates to induce the host immune response are considered as justifiable reasons for the identification of novel targets for the better management of toxoplasmosis. Thus, the identification of new critical proteins in the proteome of Toxoplasma parasites can also be helpful in designing and test more effective drugs, vaccines, and diagnostic tools. Accordingly, in this study we present important proteins found in the proteome of the life cycle-specific stages of Toxoplasma parasites that are potential diagnostic or vaccine candidates. The current study might help to understand the complexity of these parasites and provide a possible source of strategies and biomolecules that can be further evaluated in the pathobiology of Toxoplasma parasites and for diagnostics and vaccine trials against this disease.

Is There a Role for SARS-CoV-2/COVID-19 on the Female Reproductive System?

Coronavirus disease (COVID-19) has emerged as a very serious pandemic caused by the rapidly evolving transmission of the coronavirus SARS-CoV-2. Since its outbreak in 2020, the SARS CoV-2 has represented an important challenge for the physicians due to its well known respiratory sequelae. To date, the role of SARS-CoV-2 infection on organs and systems other than lungs and respiratory tract remains less clear. In particular, it remains to be investigated whether the reproductive system can be affected by the SARS-CoV-2 in the long term-period or, in alternative, drugs used to treat COVID-19 might impact the reproductive systems and, in turn, fertility. What is known is that SARS-Cov-2 binds to target cells of host through different receptors including angiotensin-converting enzyme 2 (ACE2), neuropilin-1, AXL and antibody-FcɣR complexes. ACE2 physiologically regulates both the expression of angiotensin II (Ang II) as well as Ang-(1-7) to exerts its physiological functions. The reproductive system abundantly expresses ACE2 and produces Ang-(1-7), starting from precursors which are locally generated or derived from systemic circulation. Ang-(1-7) plays an important role of stimulus to the growth and maturation of ovarian follicle as well as to ovulation. Also human endometrium expresses Ang-(1-7), mainly during the post-ovulatory phase. Animal and human observational studies demonstrated that Ang-(1-7) is involved in the maternal immune response to pregnancy and its deficiency is associated with a defective placenta development. In our manuscript, we review the current knowledge about whether SARS-CoV-2 may impact the female reproductive system. We further explain the possible molecular mechanism by which SARS-CoV-2 might affect ovarian, endometrial and female genital tract cells.

Proteomic Analysis of Sporothrix schenckii Exposed to Oxidative Stress Induced by Hydrogen Peroxide

Sporothrix schenckii modulates the expression of its cell wall proteins (CWPs) in response to reactive oxygen species (ROS) generated by the phagocytic cells of the human host, which allows it to evade and escape the immune system. In this study, we performed a comparative proteomic analysis of the CW of S. schenckii after exposure and nonexposure to H2O2. Several CWPs involved in CW remodeling and fungal pathogenesis that modulated their expression in response to this oxidizing agent were identified, as were a number of antioxidant enzymes and atypical CWPs, called moonlighting proteins, such as the Hsp70-5, lipase 1 (Lip1), enolase (Eno), and pyruvate kinase (Pk). Moreover, RT-qPCR assays demonstrated that the transcription of genes HSP70-5, LIP1, ENO, and PK is regulated in response to the oxidant. The results indicated that S. schenckii differentially expressed CWPs to confer protection against ROS upon this fungus. Furthermore, among these proteins, antioxidant enzymes and interestingly, moonlighting-like CWPs play a role in protecting the fungus from oxidative stress (OS), allowing it to infect human host cells.

Endomembrane remodeling and dynamics in Salmonella infection.

Salmonellae are bacteria that cause moderate to severe infections in humans, depending on the strain and the immune status of the infected host. These pathogens have the particularity of residing in the cells of the infected host. They are usually found in a vacuolar compartment that the bacteria shape with the help of effector proteins. Following invasion of a eukaryotic cell, the bacterial vacuole undergoes maturation characterized by changes in localization, composition and morphology. In particular, membrane tubules stretching over the microtubule cytoskeleton are formed from the bacterial vacuole. Although these tubules do not occur in all infected cells, they are functionally important and promote intracellular replication. This review focuses on the role and significance of membrane compartment remodeling observed in infected cells and the bacterial and host cell pathways involved.