Intracellular Pathogens: Host Immunity and Microbial Persistence Strategies

Abstract

Infectious diseases caused by pathogens including viruses, bacteria, fungi, and parasites are ranked as the second leading cause of death worldwide by the World Health Organization. Despite tremendous improvements in global public health since 1950, a number of challenges remain to either prevent or eradicate infectious diseases. Many pathogens can cause acute infections that are effectively cleared by the host immunity, but a subcategory of these pathogens called “intracellular pathogens” can establish persistent and sometimes lifelong infections. Several of these intracellular pathogens manage to evade the host immune monitoring and cause disease by replicating inside the host cells. These pathogens have evolved diverse immune escape strategies and overcome immune responses by residing and multiplying inside host immune cells, primarily macrophages. While these intracellular pathogens that cause persistent infections are phylogenetically diverse and engage in diverse immune evasion and persistence strategies, they share common pathogen type-specific mechanisms during host-pathogen interaction inside host cells. Likewise, the host immune system is also equipped with a diverse range of effector functions to fight against the establishment of pathogen persistence and subsequent host damage. This article provides an overview of the immune effector functions used by the host to counter pathogens and various persistence strategies used by intracellular pathogens to counter host immunity, which enables their extended period of colonization in the host. The improved understanding of persistent intracellular pathogen-derived infections will contribute to develop improved disease diagnostics, therapeutics, and prophylactics.

T Cell Immunity to Bacterial Pathogens: Mechanisms of Immune Control and Bacterial Evasion

“…For example, CD4 + T H 1 cells utilise T-bet, STAT1, and STAT4 for transcriptional regulation, produce interferon-γ (IFNγ), tumor necrosis factor-α (TNFα), interleukin-2 (IL-2), and drive cellular immune responses against intracellular pathogens, including bacteria. In contrast, CD4 + T H 2 cells promote humoral immune responses against large extracellular pathogens (e.g., parasites), are transcriptionally controlled by GATA3, STAT5, and STAT6 and produce cytokines such as IL-4, IL-5, and IL-13 [ 48 ]. As such, CD4 + T H cell subsets provide a vital source of effector cytokines that help CD8 + T cells and prime phagocytic cell subsets to kill bacteria.…”

“…MHC class II-restricted CD4 + T cells are important for protective immunity against a range of bacterial infections and provide a vital source of cytokines that help to facilitate such anti-bacterial immunity. Research on mice deficient in effector cytokines produced by CD4 + T H cell subsets [ 48 ] or humans with cytokine receptor deficiencies [ 106 ] illustrated the fundamental role that these cytokines and specific CD4 + T cell types play in this process. CD4 + T H 1 and T H 2 cells are the most categorized subsets in CD4 + T cell biology and were thought to be the only types that existed until the identification of CD4 + regulatory T cells in the early 2000s, and CD4 + T H 17 cells during 2005 and 2006 [ 4 ].…”

“…CD4 + T H 1 and T H 2 cells are the most categorized subsets in CD4 + T cell biology and were thought to be the only types that existed until the identification of CD4 + regulatory T cells in the early 2000s, and CD4 + T H 17 cells during 2005 and 2006 [ 4 ]. Unlike CD4 + T H 1 or T H 2 cells, CD4 + T H 17 cells express RORγt and STAT3 transcription factors, which control their lineage commitment and secrete IL-17A, IL-17F, and IL-22 as effector cytokines [ 48 ]. Since their identification, it has become well-known that CD4 + T H 17 cells are fundamentally important for driving immune responses against bacterial infection, along with CD4 + T H 1 subsets.…”

IL-33 Is Essential for Adjuvant Effect of Hydroxypropyl-β-Cyclodexrin on the Protective Intranasal Influenza Vaccination

“…It is well-known that IL-33 is necessary for parasite protection (48,49), but this induction of antibody production is completely controlled only by IL-33, while IL-1a, an important inflammatory cytokine in the lung (20,21), is not involved. In general, IFN and Th1 response play an important role in virus infection, but some viruses circumvent such mechanisms by various means (50). The immune defense mechanism controlled by IL-33 may be a back-up system with an alarm for cell damage by such viruses.…”

Gene Expression and Regulatory Webwork of POLR2K in Bladder Carcinogenesis by Integrated Bioinformatics Approaches

“…All of these kinases regulate mitosis, gene expression and apoptosis. Indeed, HIPK2 has been recognized as a signaling molecule which acts in various signal transduction pathways and cellular processes such as cell proliferation and apoptosis, transcriptional regulation and antiviral responses [30,31] while MAPK7 could facilitate tumor escape from immune surveillance [32,33] . Deregulated activity of HIPK2 may affect the genome integrity, leading to cancer development [34].…”