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Immunology and Microbiology · Research topic

Open research questions in Immune Response and Inflammation

42 unresolved questions extracted from the limitations and future-work sections of 171 Immune Response and Inflammation papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • Although immune cells are known to play critical roles in HTNV-induced HFRS, the detailed dynamic changes, phenotypic alterations, and functional profiles of distinct immune subsets over the course of the disease remain poorly understood.

    The role of immune cells in Hantaan-induced hemorrhagic fever with renal syndrome · 2026 · DOI

  • These find- ings collectively suggest that LPS-mediated disruption of the BNB, and associated peripheral neuropathy, is not only plausible but may be under-recognized.

    Lipopolysaccharide-mediated macrophage polarization, conserved pathogenesis, and implications for peripheral neuropathy: a systematic review · 2026 · DOI

  • Significance StatementThe embryonic origin of hematopoietic stem cells (HSCs) requires inflammatory signals, but the endogenous factor that triggers this process remains elusive.

    TLR7 Signaling Regulates Embryonic Hematopoietic Stem Cell Development by Sensing microRNA-146a in Vertebrates · 2026 · DOI

  • These findings offer a basis for developing host-response-based diagnostic signatures and further investigation of PPARG-related immunometabolic regulation in sepsis.

    Machine learning identifies PPARG as a diagnostic biomarker for sepsis linked to CD14/NF-κB signaling: integrated transcriptomics and experimental validation · 2026 · DOI

  • TLRs participate “destruction” (immune attack to pathogens and infected host cells) and “restoration” (tissue repair after damage to restore the original structure) to maintain physiological homeo- stasis. And in tumors, TLRs exhibit multifaceted roles in tumor development and TME. Many factors influence TLR functions. Here we list possible factors (include but not limited to the following aspects) and examples of how they impact TLR functions. Tumor type: while TLR5-deficiency slows down tumor progression of sarcoma and ovarian cancer in mice, it speeds up tumor progression in breast cancer (387). Cell type: while TLR3 activation induces apoptosis in malignant prostate cancer cells, it hardly elicits this effect in normal prostate epithelial cells (205); similar results are also observed in human primary and metastatic HNSCC cells, with metastatic cells more sensitive to TLR3 activation-induced apopto- in HCC cells, whereas sis (388). Sub-cellular expression site: membranous TLR3 activation hardly influences cell viability, cyto- plasmic TLR3 stimulation significantly elicits an apoptotic effect (204). Mutation of key regulators affecting TLR pathways: TLR4 activation in normal TP53 cancer cells leads to suppressed cell growth, whereas it improves cancer cell growth when TP53 is mutant (243). Ligand type: in B-cell lymphoma, while exogenous CpG ODN causes cell apoptosis via TLR9 (345), endogenous NETs released by tumor cells enhanced cell proliferation (351). Ligand concentration: while poly (I:C) used at normal concentration inhibits HCC cell growth via TLR3, lower concentration does not show a similar effect but elicits HCC invasion and metastasis (218). Stimulation tolerance: whereas primary activation of TLR7 by imidazoquinoline leads to TNF-a production by mononuclear cells, re-stimulation fails to induce the same effect within five days after the primary attempt (311). TLRs are at the top of various molecular pathways that lead to a wide range of bioactivities. They are fine regulated by multiple factors in the TME; the effects they elicit, in turn, shape the TME, thus making TLR functions in a dynamic and continuously chang- ing status. In summary, the overall effect of TLRs on a tumor is not the result of any single function induced by them. It is the result of a tune played by two powers: the power of maintaining homeostasis by the healthy host system and the power of breaking it by tumors. One power plays a “harmonious” tune (regarded as “good” or anti- tumor), while the other plays a “dissonant” tune (regarded as “bad” or pro-tumor). The multifaceted potential of TLR, such as the induction of proliferation, differentiation, apoptosis, chemotaxis, immune activation, and immune tolerance, makes the keyboard that can be utilized by both of the two powers composing their respective tunes. The distance of the final melody created (the actual body status) from harmony(homeostasis) depends on the overall influence left by the battle of “good” and “bad”, which results from the additive, synergistic, antagonistic, or abridged interactions between each note(effect) created by the two powers. Given the dual and context-dependent roles of TLRs in tumor progression, their overall effect on tumor progression represents a dynamic balance between host homeostatic regulation and tumor- driven disruption. To dissect these dual functions, advanced technol- ogies such as single-cell RNA sequencing, spatial transcriptomics, and multi-omics integration are indispensable. These approaches can resolve the cell type-specific expression and signaling landscapes of TLRs within both tumor and immune compartments, providing critical insights into their context-dependent roles (389, 390). Furthermore, coupling these findings with precision drug- targeting systems—such as nanoparticle-based or localized deliv- ery—may enable selective modulation of TLR signaling in specific cell populations (391–393).This strategy could amplify beneficial anti-tumor responses while minimizing pro-tumor or immunosup- pressive effects, representing a promising direction for next-gener- ation TLR-targeted immunotherapies.

    Toll-like receptors: versatile players in tumor · 2026 · DOI

  • Although, the intestinal injury has long been hypothesized to play a crucial role in sepsis and is frequently characterized as the “motor” of the systemic inflammatory response, the explicit mechanisms responsible for the pathogeny were not fully understood, which lead to the lack of satisfactory treatments on sepsis in clinics [2].

    Esmolol alleviates lipopolysaccharide-induced intestinal injuries by enhancing autophagy through the AMPK/mTOR/ULK1 pathway · 2026 · DOI

  • Establishing cross-scale research methods is necessary to understand how phase-separated TLR signalosomes selectively recruit or exclude specific RBP-RNA complexes.

    Toll-like receptors in innate immunity and inflammation: from fundamental biology to clinic insights · 2026 · DOI

  • However, little is known about how subsequent interaction of MoDCs with T cell-derived stimuli, such as CD40 or interferon-gamma (IFN-gamma), modulates MoDC functions.

    The influence of CD40 ligation and interferon-γ on functional properties of human monocyte-derived dendritic cells activated with polyinosinic-polycytidylic acid · 2011 · DOI

  • While we have shown that HRV16 impairs macrophage cytokine secretion, the underlying molecular mechanisms remain poorly understood.

    Human rhinovirus 16 impairs macrophage cytokine secretion by disrupting NF-κB nuclear translocation and intracellular cytokine trafficking · 2026 · DOI

  • trachomatis serovar D triggers only a weak transcriptional pro-inflammatory response, which is insufficient for the secretion of pro-inflammatory cytokines.

    Chlamydia trachomatis serovar D replicates in uroepithelial T24/83 cells in the absence of overt inflammation · 2026 · DOI

  • However, it remains unclear whether genetic variation in CXCL10 contributes to T cell dysregulation and clinical outcomes in sepsis.

    CXCL10 rs8878 identifies a genotype-associated immune phenotype linked to T-lymphocyte preservation and survival in sepsis · 2026 · DOI

  • Inflammatory signaling is pivotal for embryonic HSC development, but the mechanisms that activate it in vivo remain poorly understood.

    TLR7 Signaling Regulates Embryonic Hematopoietic Stem Cell Development by Sensing microRNA-146a in Vertebrates · 2026 · DOI

  • Despite these advancements, the specific role of TLRs in recognizing Candida albicans, a prominent human pathogen, remains elusive, warranting further investigation.

    Recent Advancements in Computational Approaches for Tailoring Toll-like Receptors and Antimicrobial Peptides Against Candida Infections · 2025 · DOI

  • Despite the considerable pathogenic impact of Candida albicans in human health, the gap in understanding the cellular recognition mechanisms and subsequent host defence activation remain insufficiently understood.

    Recent Advancements in Computational Approaches for Tailoring Toll-like Receptors and Antimicrobial Peptides Against Candida Infections · 2025 · DOI

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42 open questions have been extracted from the limitations and future-work passages of 171 Immune Response and Inflammation papers in our library. Each one below links back to the study that raised it, so you can read the original claim in context.

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