Wolbachia is one of the most widespread bacterial endosymbionts in the animal kingdom, infecting a large proportion of arthropod species. It passes from mother to offspring through the egg cytoplasm, allowing it to spread through populations without any external intervention. In many host species, Wolbachia strains induce what researchers call pathogen blocking: a phenomenon in which the presence of the bacterium reduces the ability of viruses, parasites, or other microbes to establish productive infections in the host. This property has been exploited deliberately in Aedes aegypti, the primary vector of dengue, Zika, and yellow fever, where Wolbachia strains have been artificially introduced through microinjection to create mosquito populations that are refractory to viral transmission. Field trials using this strategy have shown substantial reductions in disease incidence in several tropical regions.

What has remained less clear is how native Wolbachia infections—those that mosquitoes acquire naturally rather than through laboratory manipulation—affect host immunity and pathogen resistance. Aedes albopictus, the Asian tiger mosquito, naturally harbors Wolbachia strains that have coevolved with the species over long evolutionary timescales. Understanding whether these native infections provide meaningful protection against bacterial or viral pathogens is important both for basic immunology and for public health planning, since Ae. albopictus is a competent vector for dengue and other arboviruses and is expanding its geographic range.

To investigate these questions, the research team challenged adult female Ae. albopictus mosquitoes, both with and without their native Wolbachia infection, using sub-lethal doses of four mosquito-associated bacteria. Two of these were Gram-positive species, Micrococcus and Staphylococcus, and two were Gram-negative species, Brevundimonas and Enterobacter. The sub-lethal dosing was deliberate: rather than killing the insects outright, the exposure was designed to activate immune pathways without causing overwhelming mortality, mimicking the kind of environmental microbial encounters mosquitoes experience in nature.

When the researchers tracked post-challenge mortality over time, a clear pattern emerged. Wolbachia-infected mosquitoes showed reduced cumulative mortality and a delayed onset of age-related decline compared to their Wolbachia-free counterparts across all four bacterial challenges. However, the protective effect was not uniform. It was consistently stronger against the Gram-positive bacteria, Micrococcus and Staphylococcus, than against the Gram-negative species. This asymmetry is significant because it suggests that native Wolbachia may interact preferentially with particular arms of the insect immune system—likely the Toll pathway, which is the primary defense against Gram-positive bacteria and fungi in insects—rather than providing broad-spectrum protection.

The concept underlying these results is immune priming, a form of adaptive-like immunity in insects. Unlike vertebrates, insects lack antibodies and the classical adaptive immune system. Yet research over the past two decades has demonstrated that insects can exhibit a form of immune memory: a sub-lethal exposure to a pathogen can increase the probability of surviving a subsequent, potentially lethal challenge with the same or a related microbe. This priming effect has been documented in diverse insect orders and is thought to involve persistent changes in immune gene expression, hemocyte activity, or antimicrobial peptide levels. Wolbachia infection itself has been linked to elevated baseline immune activity in several host species, raising the possibility that the bacterium acts as a continuous immune stimulus—essentially priming the host against future microbial encounters even without an explicit prior challenge.

Building on the mortality results, the team then asked whether bacterial priming could influence the outcome of a subsequent viral infection. Mosquitoes that had been pre-challenged with the four bacteria were later fed a blood meal containing dengue virus (DENV), the oral route by which mosquitoes naturally acquire the pathogen. The results revealed a striking interaction between bacterial Gram status and viral blocking. Mosquitoes pre-challenged with the Gram-negative bacteria, Brevundimonas and Enterobacter, showed reduced DENV prevalence and lower viral loads compared to unprimed controls. In other words, a prior encounter with these environmental Gram-negative species appeared to interfere with the mosquito’s ability to support a productive dengue infection.

When the researchers examined the role of native Wolbachia in this context, they found that Wolbachia-infected mosquitoes exhibited further reductions in viral load beyond those attributable to bacterial priming alone. This additive effect suggests that native Wolbachia and bacterial priming operate through partially independent mechanisms that converge on dengue blocking. The combination of a resident endosymbiont and a recent Gram-negative bacterial exposure produced the strongest suppression of DENV observed in the study, hinting that the microbial environment inside a mosquito—shaped by both inherited symbionts and transient environmental bacteria—could meaningfully influence vector competence.

The dependence on bacterial Gram status is one of the most intriguing aspects of the findings. In Drosophila fruit flies, previous work has shown that Wolbachia-mediated pathogen blocking against bacteria occurs after oral challenge but not after systemic challenge via injection, implying that the route of exposure matters. The current study extends this picture to Ae. albopictus and to viral pathogens, showing that the protective effects of priming and Wolbachia are not uniform across microbial types. The stronger protection against Gram-positive bacteria in the mortality experiments, combined with the enhanced dengue blocking after Gram-negative priming, suggests that different immune pathways—likely the Toll pathway for Gram-positive defense and the IMD pathway for Gram-negative defense—interact differently with native Wolbachia and with subsequent viral infection.

These results carry implications for both basic science and disease control. For mosquito immunology, the study provides evidence that native Wolbachia infections in Ae. albopictus are not passive passengers but active participants in host defense, capable of reducing bacterial mortality and interacting with priming effects that depend on microbial type. For adaptive immunity in insects, the work adds to a growing body of literature showing that immune memory in these animals is real, measurable, and shaped by the resident microbiome. For public health, the findings suggest that vector competence for dengue is not a fixed property of a mosquito species but a dynamic outcome of the microbial communities it harbors. As Wolbachia-based control strategies continue to expand, understanding how native infections and environmental bacterial exposures modulate viral blocking could refine predictions about which populations will be most refractory to transmission—and could open new avenues for manipulating mosquito microbiomes to reduce arbovirus burden in endemic regions.

Subject of Research: Bacterial immune priming and Wolbachia-mediated dengue blocking in Aedes albopictus mosquitoes

Article Title: Bacterial immune priming and Wolbachia -mediated dengue blocking in Aedes albopictus mosquitoes

Article References: Alomar, A. A., Kim, D., Alto, B. W., & Caragata, E. P. (2026). Bacterial immune priming and Wolbachia-mediated dengue blocking in Aedes albopictus mosquitoes. PLOS Neglected Tropical Diseases, 20(10), e0014807. https://doi.org/10.1371/journal.pntd.0014807

Image Credits: AI Generated

DOI: 10.1371/journal.pntd.0014807

Keywords: Wolbachia, Aedes albopictus, dengue virus, immune priming, pathogen blocking, mosquito immunity, vector competence, PLOS Neglected Tropical Diseases, Bacterial, immune, priming, mediated

The stakes could hardly be higher. Global food demand is projected to rise by roughly 50 percent by 2050, yet pests and diseases already claim between 20 and 40 percent of annual crop production, at an estimated cost of around 220 billion US dollars. Conventional chemical pesticides, once the backbone of crop protection, are increasingly constrained by the evolution of resistance in pest populations, environmental persistence, residue concerns, and tightening regulatory scrutiny. Against this backdrop, the idea of enlisting microbes that live inside the plant itself—defending it from within, before, during, and after pest attack—has an obvious appeal. But as the review makes clear, appeal and reliability are very different things.

The term endophyte was coined by Anton de Bary in 1866, building on observations made decades earlier, to describe organisms living inside plant tissues without producing visible disease symptoms. Today the category spans fungi, bacteria, actinomycetes, and even archaea. In pest-resistance research, the most intensively studied groups include entomopathogenic fungi such as Beauveria and Metarhizium, which can kill insects but also colonize plant tissue, and bacterial genera such as Bacillus, Pseudomonas, and Streptomyces. Grasses host a special class of vertically transmitted fungal endophytes in the genus Epichloë, which pass from parent plant to seed and can persist across generations, producing alkaloids that deter or poison herbivores.

What makes endophytes scientifically fascinating—and commercially challenging—is that their effects are not fixed properties. The same strain may act as a mutualist, a neutral commensal, or even a latent pathogen depending on host genotype, tissue type, developmental stage, environmental conditions, and the resident microbiome. The review emphasizes that pest resistance mediated by endophytes arises through several distinct but often interacting mechanisms. Direct antagonism involves insecticidal metabolites, lytic enzymes, and toxins that reduce herbivore survival, feeding, or reproduction. Indirect mechanisms include immune priming, in which the plant’s basal defenses stay low but respond faster and more strongly when attacked; hormonal crosstalk among the jasmonic acid, salicylic acid, and ethylene signaling pathways; modification of volatile organic compound emissions that can repel herbivores or recruit predators and parasitoids; and restructuring of the plant’s internal microbial community.

Immune priming is arguably the most conceptually elegant of these mechanisms. Rather than maintaining energetically costly defenses at all times, a primed plant keeps its defensive arsenal in reserve, ready to be deployed at speed when a herbivore begins feeding. Endophyte colonization appears to establish this state of heightened preparedness through pattern-recognition signaling, calcium fluxes, reactive oxygen species, and mitogen-activated protein kinase cascades, ultimately reshaping the expression of genes for proteinase inhibitors, oxidative enzymes, phenylpropanoid metabolism, and terpenoid and alkaloid biosynthesis. Yet the review stresses that the hormonal picture is rarely simple: jasmonic acid and ethylene responses are generally associated with resistance to chewing insects, salicylic acid with biotrophic pathogens and some sap-suckers, but these pathways interact synergistically, additively, or antagonistically depending on the strain, host, pest, and environment.

The volatile dimension adds a further layer of sophistication. Endophyte-colonized plants can emit altered blends of volatile organic compounds—green leaf volatiles, terpenoids, phenylpropanoids, and benzenoids—that interfere with herbivore host-finding and attract natural enemies. In one striking example, Beauveria bassiana colonization of melon plants changed the volatile profile in ways that made the predatory lacewing Chrysoperla carnea significantly prefer aphids reared on colonized plants. Microbial volatiles emitted by the endophytes themselves, including alcohols, ketones, terpenes, acetoin, and 2,3-butanediol, may prime plant defenses or directly modify insect behavior. However, the review notes that evidence for microbially mediated volatile defense remains less mature than for general herbivore-induced plant volatiles, and stronger inference will require chemical identification of the compounds involved and behavioral assays under realistic conditions.

Perhaps the most methodologically important contribution of the review is its insistence on proving that endophytism is real before attributing pest suppression to it. Inoculation alone does not constitute proof that a microorganism has actually colonized internal plant tissues. The authors argue that rigorous studies must combine surface-sterilized tissue isolation, which yields viable strains for re-inoculation and genomic characterization; culture-independent marker-gene sequencing, which captures community composition but cannot establish viability or spatial location; shotgun metagenomics and metatranscriptomics, which reveal functional gene content and transcriptional activity; and fluorescence-based imaging, which provides the most direct spatial evidence of genuine internal residency. Only by triangulating across these approaches, and linking them explicitly to pest-performance endpoints such as survival, fecundity, feeding behavior, or tissue damage, can researchers distinguish genuine endophyte-mediated resistance from epiphytic artifacts or spurious correlations.

The evidence base, when graded by this standard, is substantial but uneven. The strongest support comes from entomopathogenic fungi such as Beauveria bassiana and Metarhizium anisopliae, which combine insect-killing capacity with endophytic colonization across multiple crops. In cotton, seed-treated B. bassiana was recovered from 35 to 55 percent of sampled tissues and significantly reduced aphid reproduction in both greenhouse and multi-season field trials—one of the few systems with genuine field validation. In tomato, integrated transcriptomic and metabolomic analyses linked whitefly resistance to 1,739 differentially expressed genes and 325 differentially abundant metabolites, implicating alkaloid biosynthesis and tryptophan metabolism. Epichloë grass endophytes offer the most chemically well-characterized protection, with alkaloids such as peramine, lolines, and ergot alkaloids reliably suppressing herbivores, but this evidence is largely confined to perennial pasture systems and does not transfer easily to annual crops.

Why, then, has so little of this promise reached the field? The review identifies a cascade of translational barriers. Colonization stability is paramount: horizontally acquired endophytes must not only enter the plant but persist at biologically relevant densities throughout the pest-vulnerable period, competing with resident microbiota and withstanding fluctuating temperatures, moisture, soil chemistry, ultraviolet exposure, and agrochemical residues. Metabolite expression is environmentally sensitive—in grass systems, alkaloid production varies with host genotype, nutrient status, drought, and even herbicide residues—so bioactivity measured under controlled conditions may not predict field efficacy. Delivery method matters enormously: seed treatments suit storage-tolerant strains, root dips favor transplanted crops, and foliar sprays face wash-off and phyllosphere competition. Formulation science, often treated as an afterthought, is in reality a determinant of biological reliability, encompassing carrier selection, encapsulation, shelf life, and compatibility with existing farm equipment.

The path forward, the authors argue, requires treating endophyte-based pest resistance as a system rather than a single mechanism. Future progress will depend on standardized efficacy testing across locations and seasons, multiomics-based mechanism validation that connects gene expression to metabolite accumulation to pest outcomes, predictive strain-selection pipelines that integrate genomic, microbiome, and environmental data, and biosafety frameworks that assess non-target effects on beneficial insects, soil communities, and vertebrate safety from the earliest stages of development. Regulatory uncertainty compounds the challenge, as endophyte products may be classified variously as microbial pesticides, biofertilizers, or biostimulants, each with different evidentiary demands. The review’s central message is ultimately one of disciplined optimism: the question is no longer whether endophytes can influence pest resistance—that is well established—but whether their effects can be made reproducible across crops, soils, climates, and management systems. Bridging that gap will require mechanism, ecology, formulation, and regulation to advance together, transforming a promising biological phenomenon into a field-ready crop-protection technology.

Subject of Research: Endophyte-mediated pest resistance in crops through direct antagonism, immune priming, volatile signaling, and microbiome modulation

Article Title: Endophyte-mediated pest resistance: mechanisms, evidence gaps, and translational opportunities

Article References: Dey Roy, S., Chatterjee, D., Thakur, R., Bhattacharya, S., Mukhopadhyay, A. K., Mondal, P., Pramanik, A., & Chatterjee, H. (2026). Endophyte-mediated pest resistance: mechanisms, evidence gaps, and translational opportunities. Frontiers in Microbiomes, 5, Article 1881416. https://doi.org/10.3389/frmbi.2026.1881416

Image Credits: AI Generated

DOI: 10.3389/frmbi.2026.1881416

Keywords: endophytes, pest resistance, biological control, entomopathogenic fungi, Beauveria bassiana, immune priming, jasmonic acid, volatile organic compounds, plant microbiome, crop protection, biopesticides, Epichloë

The research, led by Milad Ibrahim and Iman Osman along with a multidisciplinary team spanning dermatology, medical oncology, biostatistics, and population health, set out to address a persistent blind spot in cancer immunotherapy. Most studies of racial differences in melanoma outcomes have concentrated on social determinants of health, such as insurance status, geographic access to specialists, and delays in diagnosis. Those factors undeniably matter, but they leave open a fundamental question: do ancestry-associated biological differences themselves influence how patients respond to and tolerate immunotherapy? To isolate that question, the investigators designed their study around a single institution, NYU Langone Health, where patients of different ancestries were treated within the same health system and therefore had comparable access to care. That design choice is critical, because it helps separate biological variation from the socioeconomic confounders that have dominated the disparities literature.

The study enrolled 841 melanoma patients who received immune checkpoint inhibitors at Perlmutter Cancer Center, of whom 774 were non-Hispanic white and 67 were classified as underrepresented minority. Rather than relying solely on how patients described their own background, the researchers determined ancestry genetically, using whole-genome sequencing and principal component analysis to assign each patient to ancestry groups. The rigor of this approach paid off: the genetically derived ancestry assignments agreed with self-reported ancestry in 98.7 percent of cases, with an agreement coefficient of 0.99 and a 95 percent confidence interval of 0.97 to 1.00. This near-perfect concordance strengthens confidence that the ancestry categories used in the analysis reflect genuine patterns of genetic ancestry rather than misclassification, and it demonstrates that in this cohort, self-identification was a reliable proxy for genomic ancestry.

Before examining side effects, the team characterized the clinical differences between the two groups, and one demographic pattern stood out immediately. Among non-Hispanic white patients, melanoma was more prevalent in males, consistent with the well-documented male predominance of the disease in populations of European ancestry. Among underrepresented minority patients, however, melanoma was significantly more common in females, a difference that reached statistical significance with a p-value of 0.03. This reversal of the expected sex distribution hints that melanoma biology or risk factors may differ meaningfully across ancestry groups, and it adds to a growing body of evidence that melanoma in patients of African or other non-European ancestry arises in different anatomic and demographic contexts than the sun-exposure-driven disease typical of lighter-skinned populations.

The central finding of the study emerged when the researchers compared immune-related adverse events between the groups. Despite comparable melanoma stage at treatment, similar types of checkpoint inhibitor regimens, and equivalent treatment outcomes, underrepresented minority patients experienced significantly more immune-related adverse events than non-Hispanic white patients, and the difference held across all grades of toxicity. In other words, the excess toxicity was not confined to mild, easily managed side effects; it spanned the full spectrum of severity. Because the two groups were treated at the same institution and received comparable therapy, the authors argue that ancestry-associated biological factors, rather than differences in care, are the most plausible explanation for the disparity in toxicities.

To probe the biological mechanisms behind this pattern, the investigators turned their attention to autoantibodies, the immune system’s self-targeting antibodies that are thought to play a central role in immune-related adverse events. Using the KREX platform, a technology that profiles the full repertoire of autoantibodies circulating in a patient’s serum, the team compared autoantibody profiles between underrepresented minority and non-Hispanic white patients. The analysis revealed both overlapping and distinct profiles between the groups, with underrepresented minority patients exhibiting a greater number of unique autoantibodies. Crucially, these autoantibodies correlated with the development of checkpoint inhibitor toxicities, suggesting that the pre-existing or treatment-induced humoral immune landscape differs by ancestry in ways that translate directly into clinical risk.

Pathway enrichment analysis of the autoantibody targets added a mechanistic layer to the findings. The targets were significantly enriched for proteins involved in lymphocyte activation, immune signaling, and inflammatory regulation, a signature consistent with heightened immune priming and distinct humoral immune recognition in underrepresented minority patients who went on to experience immune-related adverse events. In practical terms, this means that the baseline immune state of these patients, shaped in part by their ancestry, may leave them biologically primed for the kind of overactive immune responses that checkpoint inhibitors can provoke. Toll-like receptor pathways, which act as sentinels of innate immunity, are among the immune signaling components implicated in such signatures, and their involvement fits with the idea that ancestry-linked variation in immune regulation can amplify the inflammatory consequences of releasing T cells from inhibition.

The clinical implications of the study are substantial. Immune-related adverse events are among the most important limiting factors in checkpoint inhibitor therapy: they force dose interruptions, require immunosuppressive treatment with corticosteroids or other agents, and in severe cases can permanently end immunotherapy or endanger the patient’s life. If patients of particular ancestry backgrounds carry a higher baseline risk of these toxicities, then ancestry could become a meaningful variable in clinical decision-making and risk stratification, informing how intensively patients are monitored, how early toxicities are investigated, and how treatment regimens are selected. The authors explicitly frame their conclusion in these terms, stating that the data support consideration of ancestry in clinical decision-making and risk stratification to improve both the safety and the effectiveness of immune checkpoint inhibitors in diverse patient populations.

The study also carries broader significance for the field of cancer immunotherapy research. Underrepresented minority patients remain markedly underrepresented in clinical trials of checkpoint inhibitors, which means that the safety and efficacy data guiding treatment worldwide derive disproportionately from populations of European ancestry. This study demonstrates concretely why that gap matters: a biological signal, visible in autoantibody profiles and reflected in toxicity rates, would have been invisible in a trial cohort composed only of non-Hispanic white patients. The finding that melanoma in underrepresented minority patients skews female further underscores that even the epidemiology of the disease differs across populations in ways that standard trial designs may not capture. As precision oncology moves toward tailoring treatment to individual biology, ancestry-linked immune variation is emerging as one more dimension that cannot be ignored.

There are, of course, important caveats to keep in view. The underrepresented minority group in the cohort comprised 67 patients, a substantial number for a single-institution genomic study but still modest relative to the non-Hispanic white majority, and the authors note that the work was shared early as a peer-reviewed, accepted version subject to further editorial refinement. The study was conducted within one health system in New York, and replication in other populations and geographic settings will be needed to confirm the findings and refine their generalizability. Nevertheless, the combination of rigorous genomic ancestry assignment, careful clinical phenotyping, and mechanistic autoantibody profiling makes this one of the most detailed examinations to date of how ancestry influences the tolerability of cancer immunotherapy. For a therapy class that now reaches hundreds of thousands of patients worldwide, the message is clear: the immune system’s response to having its brakes released is not universal, and understanding ancestry-linked differences in immune priming may be essential to delivering immunotherapy that is both effective and safe for everyone.

Subject of Research: The influence of patient genetic ancestry on immune-related adverse events in melanoma patients treated with immune checkpoint inhibitors

Article Title: Impact of patient ancestry on melanoma immunotherapy immune-related adverse events

Article References: Ibrahim, M., Fa’ak, F., Dutt, A., Qiu, S., Onwumere, O., Xiong, J., Ferguson, R., Ahtar, N., Pan, Y., Kim, S., Lyu, C., Zhong, J., Schober, M., Li, H., Kirchhoff, T., & Osman, I. (2026). Impact of patient ancestry on melanoma immunotherapy immune-related adverse events. Journal of Translational Medicine. https://doi.org/10.1186/s12967-026-08970-w

Image Credits: AI Generated

DOI: 10.1186/s12967-026-08970-w

Keywords: melanoma, immune checkpoint inhibitors, immune-related adverse events, ancestry, autoantibodies, health disparities, immunotherapy, whole-genome sequencing, underrepresented minorities, immune priming, precision oncology, Journal of Translational Medicine