Mandal, R. K. | Search bioRxiv

bioRxiv2021

Dynamic modulation of spleen germinal center reactions by gut bacteria during Plasmodium infection

Gut microbiota educate the local and distal immune system in early life to imprint long-term immunological outcomes while maintaining the capacity to dynamically modulate the local mucosal immune system throughout life. It is unknown if gut microbiota provide signals that dynamically regulate distal immune responses following an extra-gastrointestinal infection. Using the murine model of malaria, we show that existing spleen germinal center reactions are malleable to dynamic cues provided by gut bacteria that impact parasite burden. Gut bacteria composition was also shown to correlate with the severity of malaria in humans. Whereas antibiotic-induced changes in gut bacteria has been associated with immunopathology or impairment of immunity, our data demonstrate antibiotic-induced changes in gut bacteria can enhance humoral immunity to Plasmodium. This effect is not universal, but depends on baseline gut bacteria composition. These data demonstrate the dynamic communications that exist between gut bacteria and the systemic immune system as well as the plasticity of an ongoing humoral immune response. SummaryThe study by Mandal R, et al. provides new insight into the dynamic communications that exist between gut bacteria, the systemic immune system and the plasticity of spleen germinal center reactions during Plasmodium infection.

immunology↗

bioRxiv2019

Genetic determinants in Salmonella enterica serotype Typhimurium required for overcoming stressors in the host environment

Salmonella enterica serovar Typhimurium (S. Typhimurium), a non-typhoidal Salmonella (NTS), result in a range of diseases, including self-limiting gastroenteritis, bacteremia, enteric fever, and focal infections representing a major disease burden worldwide. There is still a significant portion of Salmonella genes whose functional basis to overcome host innate defense mechanisms, consequently causing disease in host, largely remains unknown. Here, we have applied a high-throughput transposon sequencing (Tn-seq) method to unveil the genetic factors required for the growth or survival of S. Typhimurium under various host stressors simulated in vitro. A highly saturating Tn5 library of S. Typhimurium 14028s was subjected to selection during growth in the presence of short chain fatty acid (100 mM propionate), osmotic stress (3% NaCl) or oxidative stress (1 mM H2O2) or survival in extreme acidic pH (30 min in pH3) or starvation (12 days in 1X PBS). We have identified an overlapping set of 339 conditionally essential genes (CEGs) required by S. Typhimurium to overcome these host insults. Interestingly, entire eight genes encoding F0F1-ATP synthase subunit proteins were required for fitness in all five stresses. Intriguingly, total 88 genes in Salmonella pathogenicity island (SPI), including SPI-1, SPI-2, SPI-3, SPI-5, SPI-6 and SPI-11 are also required for fitness under the in vitro conditions evaluated in this study. Additionally, by comparative analysis of the genes identified in this study and the genes previously shown to be required for in vivo fitness, we identified novel genes (marBCT, envF, barA, hscA, rfaQ, rfbI and putative proteins STM14_1138, STM14_3334, STM14_4825, and STM_5184) that has compelling potential to be exploited as vaccine development and/or drug target to curb the Salmonella infection.

microbiology↗