Body's response to different strains of tuberculosis could affect
transmission
Study could shed light on disease spread, development of resistance

Date:
April 16, 2022
Source:
Rutgers University
Summary:
Two strains of the bacterium causing tuberculosis have only minor
genetic differences but attack the lungs in completely different
fashion, according to researchers.



FULL STORY ==========================================================================
Two strains of the bacterium causing tuberculosis have only minor
genetic differences but attack the lungs in completely different fashion, according to Rutgers researchers.


==========================================================================
The findings, published in the journal Nature Communications, could
help break the cycle of rapid transmission of TB, the second-leading
infectious killer in the world after COVID-19, according to the World
Health Organization. The disease mechanisms uncovered in the study
could also provide answers about why treatments work in some patients
but not others.

"These findings implicate strain differences as having an important
effect on the response of lung alveolar macrophages and how tuberculosis manifests itself in the body and how it is transmitted," said study
author Padmini Salgame, associate director of the Public Health Research Institute at Rutgers New Jersey Medical School. "We also believe it will
inform anyone hoping to devise more effective treatments." To better understand transmission and how it relates to treatment outcomes, the researchers focused on the impact these two strains of Mycobacterium tuberculosis have on the lungs. Though the strains differ slightly in
their gene sequences, one is regarded as "high transmission" because it
spreads easily and the second as "low transmission" because it does not
infect as readily. TB bacteria are spread through the air when persons
with TB disease in their lungs cough, speak or even sing.

Using strains identified in a Rutgers collaborative study with
researchers at Nu'cleo de Doenc,as Infecciosas (NDI)in Brazil comparing
"high transmission" and "low transmission" households of people with TB,
the scientists studied the immune pathways that the pathogen triggered
in the lungs of the infected mice.

In mice infected with the high transmission strain, their lungs quickly
formed clumps of immune cells known as granulomas that encased the
invading bacteria, stopping development of a more virulent disease. In
most cases, the granulomas broke down eventually, spilling their
contents. Researchers believe that if the escaped bacteria are close
enough to the bronchial airway, they could be expelled into the air as infectious aerosols.

"By inducing granulomas with the potential to develop into cavitary
lesions that aids bacterial escape into the airways, high transmission
M. tuberculosis strains are poised for greater transmissibility," said
Salgame, who is also a professor in the Department of Medicine.

In mice infected with the low transmission strain, the invading bacteria
were slow to activate the lung alveolar macrophages and ended up producing patches of inflammation within the lungs that did not allow the bacteria
to escape into airways and allowed them to conglomerate and intensify
the infection, Salgame said.

The discovery of the different trajectories taken by the strains gives
hope to new approaches to stopping transmission and treatment.

"We have long known that some individuals with TB are more infectious than others," Salgame said. "However, until now, the mechanisms responsible
for this variability in transmission between individuals with TB have not
been well understood." Other Rutgers authors included Arianne Lovey,
Sheetal Verma, Vaishnavi Kaipilyawar and Jerrold Ellner, all at the
Center for Emerging Pathogens, and Seema Husain of The Genomics Center.


========================================================================== Story Source: Materials provided by Rutgers_University. Original written
by Kitta MacPherson.

Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Arianne Lovey, Sheetal Verma, Vaishnavi Kaipilyawar, Rodrigo
Ribeiro-
Rodrigues, Seema Husain, Moises Palaci, Reynaldo Dietze, Shuyi Ma,
Robert D. Morrison, David. R. Sherman, Jerrold J. Ellner, Padmini
Salgame. Early alveolar macrophage response and IL-1R-dependent
T cell priming determine transmissibility of Mycobacterium
tuberculosis strains. Nature Communications, 2022; 13 (1) DOI:
10.1038/s41467-022-28506-2 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/04/220416161124.htm

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